<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03297177</url>
  </required_header>
  <id_info>
    <org_study_id>GARM NDD</org_study_id>
    <nct_id>NCT03297177</nct_id>
  </id_info>
  <brief_title>Autologous Stem/Stromal Cells in Neurological Disorders and Disease</brief_title>
  <acronym>NDD</acronym>
  <official_title>Use Of Autologous Stem Cell Use In Neurological Non-neoplastic Disorders And Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regeneris Medical</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Global Alliance for Regenerative Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Robert W. Alexander, MD, FICS</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Regeneris Medical Inc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Regeneris Medical</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study deals with evaluation of safety and efficacy of use of stem/stromal cell isolates&#xD;
      from autologous microvasculature in neurological, non-neoplastic disease. Autologous cells&#xD;
      are acquired via microcannula aspiration of subdermal fat deposits, isolated through a&#xD;
      digestive process, and concentrated via standard centrifugation. The cellular stromal&#xD;
      vascular fraction (cSVF) created is neutralized and rinsed to eliminate residual enzymatic&#xD;
      molecules.&#xD;
&#xD;
      These cells are suspending in sterile Normal Saline Solution (500cc) and re-administered via&#xD;
      an intravenous parenteral route, passed through a standard sterile 150 u (micron) filter in&#xD;
      line.&#xD;
&#xD;
      Multiple tracking and questionnaire followup is intended over a 5 year period, with objective&#xD;
      and subjective criteria being met. Compilation and analysis of data to be completed after&#xD;
      that period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dementia refers to neurodegenerative conditions causing gradual decrease in ability to think&#xD;
      and recall, to the point that is impacts daily functions. It is often accompanied by language&#xD;
      difficulties, wide ranging emotional issues, loss of language skills, and lowering of&#xD;
      activity motivation. These changes are often in the face of unchanged consciousness.&#xD;
&#xD;
      Most common type is Alzheimer's Disease (50-70% of cas.es), but include vascular dementia&#xD;
      (25%), Lewy Body dementia (15%) and frontotemporal dementia. There are many interrelated&#xD;
      disorders that mask the underlying issues, such as in Parkinson's Disease, and whose&#xD;
      diagnosis may overlap with the others.&#xD;
&#xD;
      Most common symptoms include memory lapses, visual-spatial language changes, attention loss&#xD;
      and problem solving difficulties. A wide variety of other symptoms may be seen, such as&#xD;
      balance issues, tremors, difficulty swallowing, hallucinations, wandering, restlessness or&#xD;
      agitation/depression, mood swings, etc..&#xD;
&#xD;
      Parkinson's Disease (PD) is a long-term neurodegenerative disorder of the Central Nervous&#xD;
      System (CNS) that usually impacts the motor system, in a progressive and long-term fashion.&#xD;
      Early signs include tremors, rigidity, slow movements and walking issues. It is often&#xD;
      associated with thinking problems and depression, plus emotional states that impact daily&#xD;
      living.&#xD;
&#xD;
      The causation of PD is felt to involve genetic predisposition and environmental factors.&#xD;
      History of head injuries, chemical exposures, smokers, caffeine intake and other dietary&#xD;
      issues. The motor symptoms seem to result from cellular death in the midbrain area&#xD;
      (particularly the substantia nigra) and associated with inadequate dopamine. Plaques (protein&#xD;
      build up following cellular death) may be a prominent feature, and use of neuroimaging (like&#xD;
      MRI with/without contrast) is of value to track progressive changes in the brain.&#xD;
&#xD;
      Conventional therapy is use of L-DOPA and dopamine agonists and pharmaceutical agents have&#xD;
      not proved of long-term reversal or arrest of the process. Evaluation of non-traditional&#xD;
      methods are currently gaining popularity, especially in the area of stem/stromal cellular&#xD;
      therapy.&#xD;
&#xD;
      CNS Autoimmune Demyelination is group of disorders of the CNS which feature loss of myelin&#xD;
      from unknown causes but include variants of encephalomyelitis, cerebral sclerosis of&#xD;
      Schilder, multiple sclerosis, and idiopathic inflammatory demyelination.&#xD;
&#xD;
      In cases involving myelin sheath of neurons is damaged, reducing the conduction of nerve&#xD;
      signals causing loss of sensory, motor, cognitive abilities, and a wide variety of functions&#xD;
      dependent on actual location of changes.&#xD;
&#xD;
      There is strong evidence that autoimmune, infectious agents, and chemical reactions may&#xD;
      contribute to the evolution of the disease complex. In cases of multiple sclerosis, it&#xD;
      appears that T-cells and macrophages, and mast cells may be present in the CNS plaques that&#xD;
      are characteristically seen in areas of the ventricles and scattered areas of the brain.&#xD;
      These are typically identified and tracked by MRI studies.&#xD;
&#xD;
      Traditional pharmaceutical approaches have proven to be of little advantage in reversing or&#xD;
      completely stopping the disease processes. Many side effects and reactions, or loss of drug&#xD;
      effectiveness have led researchers to explore use of stem/stromal cells with their effects on&#xD;
      immunomodulation and inflammatory modulation effects. Early trials suggest that these may be&#xD;
      able to actually reverse visible lesions and improve quality of function and life, with&#xD;
      reported improvement in neurological conditions.&#xD;
&#xD;
      Management of symptoms is often accompanied by lifestyle changes, rest periods, physical and&#xD;
      mental rehabilitations, diet, chelation and hyper-vitamin infusions, and a number of&#xD;
      antioxidant therapies. The progressive phases seem to include the innate immune system, and&#xD;
      is felt to explain the potential value of use of autologous stem/stromal cellular groups,&#xD;
      particularly involving the mesenchymal and pericytic/endothelial cellular groups.&#xD;
&#xD;
      Sensorimotor demyelination neuropathies (HMSN) is group of neuropathies characterized by&#xD;
      impact on afferent and efferent neural communications. They feature atypical neural&#xD;
      development and degradation of nerve tissues.&#xD;
&#xD;
      Two common forms of HMSN are either hypertrophic demyelinated nerves or atrophy of nerve&#xD;
      (peripheral) and neural tissues. Hypertrophy is featured by neural stiffness rather than&#xD;
      demyelination of peripheral nerves. Whereas atrophy causes loss of axons and neural cell&#xD;
      bodies. They often experience progressive muscle atrophy and sensory neuropathy of the&#xD;
      extremities. The term &quot;hereditary motor and sensory neuropathy has been commonly referred to&#xD;
      a forms of Charcot-Marie-Tooth Disease (CMT). There are distinct genetic and phenotypically&#xD;
      distinct forms of CMT, and the term of HMSN is less frequently used.&#xD;
&#xD;
      Usual onset is childhood or young adulthood, with motor involvement more prominent that&#xD;
      sensory. Often mistaken for causalgia or fibromyalgia, the symptoms of fatigue, pain, balance&#xD;
      loss, areflexia, visual changes, foot drop and scoliosis. As in the causalgia or Sympathetic&#xD;
      Reflex Dystrophy (SRD), these patients are treated according to symptoms, with medication and&#xD;
      traditional interventions proving of limited benefit. Some preliminary findings using the&#xD;
      modulatory action of stem/stromal cells suggest some help with the symptomatology,&#xD;
      particularly relative fatigue and pain.&#xD;
&#xD;
      Huntington's Disease is an inherited disorder resulting in death of brain cells. A gradual&#xD;
      change in mood or mental abilities, is followed by unsteady gait, jerky body movements,&#xD;
      leading to speech loss or severe depression. Although associated with heredity or mutation,&#xD;
      pharmaceuticals and stem/stromal cell therapy are felt to offer some assistance in&#xD;
      maintaining quality of life (Qol).&#xD;
&#xD;
      The huntington protein (HP) is poorly understood, but believe toxic to certain cell types,&#xD;
      particularly in the brain. Damage is most noticed in the striatum of the brain. The changes&#xD;
      associated with the HP relate to the cell transcription, cell signaling and intracellular&#xD;
      transport.&#xD;
&#xD;
      Most prominent changes are within the basal ganglia (neostriatum) and includes the caudate&#xD;
      nucleus and putamen. Substantia nigra and cerebellum seem particularly impacted. Physical&#xD;
      therapy, occupational therapy and speech therapy have been used in conjunction with trials&#xD;
      using autologous stem/stromal cellular therapies are offering some slowing of the processes.&#xD;
&#xD;
      Medications have been developed, but remain modestly effective and possessing major side&#xD;
      effects and poorly tolerated. Most of the pharmaceutical approaches have not proven effective&#xD;
      in reversal of the disease, many accepting a slowing or remission induction without inducing&#xD;
      the body ability to provide any regenerative effects. Dietary controls, use of mind&#xD;
      exercising, hyperoxygenation protocols, chelation, vitamin infusions, etc. have proven to be&#xD;
      helpful adjunctive therapies. Alternative treatments, including physical therapy and some&#xD;
      stem/stromal therapies have become more common.&#xD;
&#xD;
      Three main characteristics of the neurodegenerative group are: 1). Lesion formations in the&#xD;
      central nervous system (called Plaques); 2). Inflammation; 3). Demyelination and Destruction&#xD;
      of myelin sheaths of neurons. This demyelination is thought to stimulate the inflammatory&#xD;
      processes due to action of a lymphocyte group known at T-cell which seems to recognize&#xD;
      patient's own myelin as foreign and proceeds to attack it (known as &quot;autoreactive&#xD;
      lymphocytes&quot;). These findings are often concluded to represent an autoimmune response to&#xD;
      one's own tissues. The inherent properties of modulation and inflammatory modulation make&#xD;
      potential uses of autologous reparative group of cells located throughout the body in&#xD;
      association with microcapillary structures in essentially every tissue in the body. These&#xD;
      cells have been identified by cell surface markers and studied in tissue culture to have&#xD;
      &quot;multipotent&quot; capabilities that potentially participate in the regenerative processes to help&#xD;
      arrest or improve the autoimmune group of disorders.&#xD;
&#xD;
      Traditionally, exacerbation's are often treated with high dose intravenous steroids which may&#xD;
      be of short term reduction of symptoms, not addressing the underlying causation. Current&#xD;
      medications available for treatment are expensive an fraught with major side effects, making&#xD;
      their use very difficult and producing limited measured value.&#xD;
&#xD;
      With the advent of convenient ability to acquire significant numbers of alive (viable) an&#xD;
      easily gathered by harvesting from microvascular stores in the body (adipose tissue complex).&#xD;
      Technological advances in sterile, closed processing, has provided the ability to easily and&#xD;
      safely acquire significant of stem/stromal cells for use in clinical studies.&#xD;
&#xD;
      This study is aimed at evaluation of the safety profile (adverse reactions &amp; severe adverse&#xD;
      reactions) of the closed syringe, microcannula harvesting of subdermal fat deposits (largest&#xD;
      known source of microvascular tissues in the body). This autologous cell group obtained with&#xD;
      isolation and concentration of cells within the stromal vascular fraction (SVF) via enzymatic&#xD;
      digestion, and deployed via intravascular r rebral fluids in defects of the blood brain&#xD;
      barrier (BBB) or are small enough to pass into the fluids of the CNS (central nervous&#xD;
      system). Effects are believed to be a function of both cellular multipotent abilities, but&#xD;
      also regards the autocrine/paracrine secretory capacity of the cell group within the body.&#xD;
      The body has the ability to request (chemotaxis) certain needed cellular and secreted&#xD;
      chemicals to help healing and regeneration. Current thought are trending that the secretions&#xD;
      may, in fact, be more important to the reparative and regenerative processes than the&#xD;
      cellular contributions.&#xD;
&#xD;
      In this study, disorders which involve autoimmune and inflammatory changes that impact the&#xD;
      brain and nervous system are to be study, tracked and reported over time to determine&#xD;
      ultimate efficacy and the &quot;interval&quot; therapy needs (or lack thereof) to maintain the&#xD;
      accomplished arrest or improvement in the underlying tissues. Currently these intervals are&#xD;
      examined by brain magnetic resonance imaging (MRI) with and without contrast. Correlation of&#xD;
      image changes and clinical function will be made with subjective Quality of Life (Qol) and&#xD;
      diary type observations by patients and caregivers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 1, 2020</start_date>
  <completion_date type="Anticipated">January 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participant with adverse events (AE) or severe adverse events (SAE)</measure>
    <time_frame>6 month intervals for up to 5 years</time_frame>
    <description>Activities of Daily Living (ADL)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Neurological Function</measure>
    <time_frame>6 month Intervals for up to 5 years</time_frame>
    <description>Change from baseline of deficits of neurologic function identified by patient as impaired prior to study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological Tested Functions</measure>
    <time_frame>6 month interval for up to 5 years</time_frame>
    <description>Change from baseline of deficits of neurological function identified by medical provider as impaired prior to study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Magnetic Resonance Imaging (MRI)</measure>
    <time_frame>6 month intervals for up to 5 years</time_frame>
    <description>Change in baseline of MRI with and without contrast at 6 month intervals</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Dementia</condition>
  <condition>Parkinson</condition>
  <condition>Altered Behavior in Alzheimer Disease</condition>
  <condition>Demyelinating Autoimmune Diseases, CNS</condition>
  <condition>Demyelinating Sensorimotor Neuropathy</condition>
  <condition>Corticobasal Degeneration</condition>
  <arm_group>
    <arm_group_label>Microcannula Harvest Adipose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acquisition AD-tSVF Via Closed Syringe Microcannula</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Centricyte 1000</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous Adipose-Derived Tissue Stromal Vascular Fraction (tSVF) via enzymatic digestive isolation &amp; concentration in Centricyte 1000 closed system to create AD-cSVF</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sterile Normal Saline Infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sterile Normal Saline to Re-Suspend Autologous cSVF pellet for delivery via intravascular (IV) route</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Microcannula Harvest Adipose</intervention_name>
    <description>Use Closed Syringe Microcannula Harvest Adipose, Autologous Subdermal Deposits</description>
    <arm_group_label>Microcannula Harvest Adipose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Centricyte 1000</intervention_name>
    <description>Closed System, Digestive Isolation &amp; Concentration of AD-cSVF</description>
    <arm_group_label>Centricyte 1000</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sterile Normal Saline Infusion</intervention_name>
    <description>Sterile Normal Saline Re-Suspension of cSVF and Delivery of AD-cSVF via IV route</description>
    <arm_group_label>Sterile Normal Saline Infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented Functional Neurological Damage To Central or Peripheral Nervous System&#xD;
             Unlikely To Improve With Present Standard of Care Approaches&#xD;
&#xD;
          -  At least 6 months after onset or diagnosis of disease process&#xD;
&#xD;
          -  Current Medical therapy for the condition is either failing or not tolerated by&#xD;
             patient&#xD;
&#xD;
          -  Patient must be capable of interval neurologic exams with investigators or their own&#xD;
             neurologic specialists&#xD;
&#xD;
          -  Patient must be capable and determined competent to provide detailed informed consent&#xD;
             for study participation&#xD;
&#xD;
          -  In estimation of investigators, that there are minimal or no significant risk of harm&#xD;
             to general health or conditions for collection of autologous stem cell collection and&#xD;
             use&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability of patient to have diagnostic examinations or studies (MRI) to evaluate and&#xD;
             document the disease state or unwilling/unable to cooperate with such documentation&#xD;
&#xD;
          -  Patients not medically stable, or whom may have ongoing conditions which increases may&#xD;
             place the patient at significant risk of major complications, to be determined by&#xD;
             investigator or patient's medical provider or neurologic specialists&#xD;
&#xD;
          -  History of active cancer or ongoing anticancer therapy within six months of such care&#xD;
&#xD;
          -  Women of childbearing age must not be pregnant at the time of treatment, and should&#xD;
             refrain from becoming pregnant of at minimum of 3 month after study treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ryan Welter, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Regeneris Medical Inc</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Glenn C Terry</last_name>
    <role>Principal Investigator</role>
    <affiliation>Global Alliance for Regenerative Medicine (GARM)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert W Alexander, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Healeon Medical</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ryan Welter, MD, PhD</last_name>
    <phone>508.345.5492</phone>
    <email>r.welter@regenerismedical.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kristin Corrado</last_name>
    <phone>508.316.4268</phone>
    <email>k.corrado@regenerismedical.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Regeneris Medical Inc</name>
      <address>
        <city>North Attleboro</city>
        <state>Massachusetts</state>
        <zip>02760</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Ryan Welter, MD, PhD</last_name>
      <phone>508-345-5492</phone>
      <email>r.welter@regenerismedical.com</email>
    </contact>
    <contact_backup>
      <last_name>Kristin Corrado</last_name>
      <phone>508.316.4268</phone>
      <email>k.corrado@regenerismedical.com</email>
    </contact_backup>
    <investigator>
      <last_name>Ryan Welter, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Robert W Alexander, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Glenn C Terry, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Regeneris Medical</name>
      <address>
        <city>North Attleboro</city>
        <state>Massachusetts</state>
        <zip>02760</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Ryan Welter, MD, PhD</last_name>
      <phone>508-316-4268</phone>
      <email>k.corrado@regenerismedical.com</email>
    </contact>
    <contact_backup>
      <last_name>Kristin Corrado</last_name>
      <phone>508.316.4268</phone>
      <email>k.corrado@regenerismedical.com</email>
    </contact_backup>
    <investigator>
      <last_name>Glenn C Terry, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Robert W Alexander, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ryan Welter, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Honduras</country>
  </removed_countries>
  <reference>
    <citation>Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, Lai EC, Verny M, Ray-Chaudhuri K, McKee A, Jellinger K, Pearce RK, Bartko JJ. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology. 1997 Jan;48(1):119-25. doi: 10.1212/wnl.48.1.119.</citation>
    <PMID>9008506</PMID>
  </reference>
  <reference>
    <citation>Rizzo G, Martinelli P, Manners D, Scaglione C, Tonon C, Cortelli P, Malucelli E, Capellari S, Testa C, Parchi P, Montagna P, Barbiroli B, Lodi R. Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease. Brain. 2008 Oct;131(Pt 10):2690-700. doi: 10.1093/brain/awn195. Epub 2008 Sep 26.</citation>
    <PMID>18819991</PMID>
  </reference>
  <reference>
    <citation>Alladi S, Xuereb J, Bak T, Nestor P, Knibb J, Patterson K, Hodges JR. Focal cortical presentations of Alzheimer's disease. Brain. 2007 Oct;130(Pt 10):2636-45. doi: 10.1093/brain/awm213.</citation>
    <PMID>17898010</PMID>
  </reference>
  <reference>
    <citation>Sha SJ, Ghosh PM, Lee SE, Corbetta-Rastelli C, Jagust WJ, Kornak J, Rankin KP, Grinberg LT, Vinters HV, Mendez MF, Dickson DW, Seeley WW, Gorno-Tempini M, Kramer J, Miller BL, Boxer AL, Rabinovici GD. Predicting amyloid status in corticobasal syndrome using modified clinical criteria, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography. Alzheimers Res Ther. 2015 Mar 2;7(1):8. doi: 10.1186/s13195-014-0093-y. eCollection 2015.</citation>
    <PMID>25733984</PMID>
  </reference>
  <reference>
    <citation>Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76. doi: 10.1136/jnnp.2007.131045.</citation>
    <PMID>18344392</PMID>
  </reference>
  <reference>
    <citation>Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745-52. doi: 10.1136/jnnp.51.6.745.</citation>
    <PMID>2841426</PMID>
  </reference>
  <reference>
    <citation>Pedrosa DJ, Timmermann L. Review: management of Parkinson's disease. Neuropsychiatr Dis Treat. 2013;9:321-40. doi: 10.2147/NDT.S32302. Epub 2013 Mar 3.</citation>
    <PMID>23487540</PMID>
  </reference>
  <reference>
    <citation>Mayo L, Quintana FJ, Weiner HL. The innate immune system in demyelinating disease. Immunol Rev. 2012 Jul;248(1):170-87. doi: 10.1111/j.1600-065X.2012.01135.x.</citation>
    <PMID>22725961</PMID>
  </reference>
  <reference>
    <citation>Ransohoff RM, Howe CL, Rodriguez M. Growth factor treatment of demyelinating disease: at last, a leap into the light. Trends Immunol. 2002 Nov;23(11):512-6. doi: 10.1016/s1471-4906(02)02321-9.</citation>
    <PMID>12401395</PMID>
  </reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 26, 2017</study_first_submitted>
  <study_first_submitted_qc>September 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 29, 2017</study_first_posted>
  <last_update_submitted>October 17, 2018</last_update_submitted>
  <last_update_submitted_qc>October 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Healeon Medical Inc</investigator_affiliation>
    <investigator_full_name>Ryan Welter, MD, PhD</investigator_full_name>
    <investigator_title>Principal Investigator, Science</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Corticobasal Degeneration</mesh_term>
    <mesh_term>Demyelinating Autoimmune Diseases, CNS</mesh_term>
    <mesh_term>Autoimmune Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Annual Summary of Enrolled Cases By All collaborators, principle investigators, or accept sub-investigators</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03297177
org study id: GARM NDD
nct id: NCT03297177
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The study deals with evaluation of safety and efficacy of use of stem/stromal cell isolates
      from autologous microvasculature in neurological, non-neoplastic disease. Autologous cells
      are acquired via microcannula aspiration of subdermal fat deposits, isolated through a
      digestive process, and concentrated via standard centrifugation. The cellular stromal
      vascular fraction (cSVF) created is neutralized and rinsed to eliminate residual enzymatic
      molecules.

      These cells are suspending in sterile Normal Saline Solution (500cc) and re-administered via
      an intravenous parenteral route, passed through a standard sterile 150 u (micron) filter in
      line.

      Multiple tracking and questionnaire followup is intended over a 5 year period, with objective
      and subjective criteria being met. Compilation and analysis of data to be completed after
      that period.
Dementia refers to neurodegenerative conditions causing gradual decrease in ability to think
      and recall, to the point that is impacts daily functions. It is often accompanied by language
      difficulties, wide ranging emotional issues, loss of language skills, and lowering of
      activity motivation. These changes are often in the face of unchanged consciousness.

      Most common type is Alzheimer's Disease (50-70% of cas.es), but include vascular dementia
      (25%), Lewy Body dementia (15%) and frontotemporal dementia. There are many interrelated
      disorders that mask the underlying issues, such as in Parkinson's Disease, and whose
      diagnosis may overlap with the others.

      Most common symptoms include memory lapses, visual-spatial language changes, attention loss
      and problem solving difficulties. A wide variety of other symptoms may be seen, such as
      balance issues, tremors, difficulty swallowing, hallucinations, wandering, restlessness or
      agitation/depression, mood swings, etc..

      Parkinson's Disease (PD) is a long-term neurodegenerative disorder of the Central Nervous
      System (CNS) that usually impacts the motor system, in a progressive and long-term fashion.
      Early signs include tremors, rigidity, slow movements and walking issues. It is often
      associated with thinking problems and depression, plus emotional states that impact daily
      living.

      The causation of PD is felt to involve genetic predisposition and environmental factors.
      History of head injuries, chemical exposures, smokers, caffeine intake and other dietary
      issues. The motor symptoms seem to result from cellular death in the midbrain area
      (particularly the substantia nigra) and associated with inadequate dopamine. Plaques (protein
      build up following cellular death) may be a prominent feature, and use of neuroimaging (like
      MRI with/without contrast) is of value to track progressive changes in the brain.

      Conventional therapy is use of L-DOPA and dopamine agonists and pharmaceutical agents have
      not proved of long-term reversal or arrest of the process. Evaluation of non-traditional
      methods are currently gaining popularity, especially in the area of stem/stromal cellular
      therapy.

      CNS Autoimmune Demyelination is group of disorders of the CNS which feature loss of myelin
      from unknown causes but include variants of encephalomyelitis, cerebral sclerosis of
      Schilder, multiple sclerosis, and idiopathic inflammatory demyelination.

      In cases involving myelin sheath of neurons is damaged, reducing the conduction of nerve
      signals causing loss of sensory, motor, cognitive abilities, and a wide variety of functions
      dependent on actual location of changes.

      There is strong evidence that autoimmune, infectious agents, and chemical reactions may
      contribute to the evolution of the disease complex. In cases of multiple sclerosis, it
      appears that T-cells and macrophages, and mast cells may be present in the CNS plaques that
      are characteristically seen in areas of the ventricles and scattered areas of the brain.
      These are typically identified and tracked by MRI studies.

      Traditional pharmaceutical approaches have proven to be of little advantage in reversing or
      completely stopping the disease processes. Many side effects and reactions, or loss of drug
      effectiveness have led researchers to explore use of stem/stromal cells with their effects on
      immunomodulation and inflammatory modulation effects. Early trials suggest that these may be
      able to actually reverse visible lesions and improve quality of function and life, with
      reported improvement in neurological conditions.

      Management of symptoms is often accompanied by lifestyle changes, rest periods, physical and
      mental rehabilitations, diet, chelation and hyper-vitamin infusions, and a number of
      antioxidant therapies. The progressive phases seem to include the innate immune system, and
      is felt to explain the potential value of use of autologous stem/stromal cellular groups,
      particularly involving the mesenchymal and pericytic/endothelial cellular groups.

      Sensorimotor demyelination neuropathies (HMSN) is group of neuropathies characterized by
      impact on afferent and efferent neural communications. They feature atypical neural
      development and degradation of nerve tissues.

      Two common forms of HMSN are either hypertrophic demyelinated nerves or atrophy of nerve
      (peripheral) and neural tissues. Hypertrophy is featured by neural stiffness rather than
      demyelination of peripheral nerves. Whereas atrophy causes loss of axons and neural cell
      bodies. They often experience progressive muscle atrophy and sensory neuropathy of the
      extremities. The term "hereditary motor and sensory neuropathy has been commonly referred to
      a forms of Charcot-Marie-Tooth Disease (CMT). There are distinct genetic and phenotypically
      distinct forms of CMT, and the term of HMSN is less frequently used.

      Usual onset is childhood or young adulthood, with motor involvement more prominent that
      sensory. Often mistaken for causalgia or fibromyalgia, the symptoms of fatigue, pain, balance
      loss, areflexia, visual changes, foot drop and scoliosis. As in the causalgia or Sympathetic
      Reflex Dystrophy (SRD), these patients are treated according to symptoms, with medication and
      traditional interventions proving of limited benefit. Some preliminary findings using the
      modulatory action of stem/stromal cells suggest some help with the symptomatology,
      particularly relative fatigue and pain.

      Huntington's Disease is an inherited disorder resulting in death of brain cells. A gradual
      change in mood or mental abilities, is followed by unsteady gait, jerky body movements,
      leading to speech loss or severe depression. Although associated with heredity or mutation,
      pharmaceuticals and stem/stromal cell therapy are felt to offer some assistance in
      maintaining quality of life (Qol).

      The huntington protein (HP) is poorly understood, but believe toxic to certain cell types,
      particularly in the brain. Damage is most noticed in the striatum of the brain. The changes
      associated with the HP relate to the cell transcription, cell signaling and intracellular
      transport.

      Most prominent changes are within the basal ganglia (neostriatum) and includes the caudate
      nucleus and putamen. Substantia nigra and cerebellum seem particularly impacted. Physical
      therapy, occupational therapy and speech therapy have been used in conjunction with trials
      using autologous stem/stromal cellular therapies are offering some slowing of the processes.

      Medications have been developed, but remain modestly effective and possessing major side
      effects and poorly tolerated. Most of the pharmaceutical approaches have not proven effective
      in reversal of the disease, many accepting a slowing or remission induction without inducing
      the body ability to provide any regenerative effects. Dietary controls, use of mind
      exercising, hyperoxygenation protocols, chelation, vitamin infusions, etc. have proven to be
      helpful adjunctive therapies. Alternative treatments, including physical therapy and some
      stem/stromal therapies have become more common.

      Three main characteristics of the neurodegenerative group are: 1). Lesion formations in the
      central nervous system (called Plaques); 2). Inflammation; 3). Demyelination and Destruction
      of myelin sheaths of neurons. This demyelination is thought to stimulate the inflammatory
      processes due to action of a lymphocyte group known at T-cell which seems to recognize
      patient's own myelin as foreign and proceeds to attack it (known as "autoreactive
      lymphocytes"). These findings are often concluded to represent an autoimmune response to
      one's own tissues. The inherent properties of modulation and inflammatory modulation make
      potential uses of autologous reparative group of cells located throughout the body in
      association with microcapillary structures in essentially every tissue in the body. These
      cells have been identified by cell surface markers and studied in tissue culture to have
      "multipotent" capabilities that potentially participate in the regenerative processes to help
      arrest or improve the autoimmune group of disorders.

      Traditionally, exacerbation's are often treated with high dose intravenous steroids which may
      be of short term reduction of symptoms, not addressing the underlying causation. Current
      medications available for treatment are expensive an fraught with major side effects, making
      their use very difficult and producing limited measured value.

      With the advent of convenient ability to acquire significant numbers of alive (viable) an
      easily gathered by harvesting from microvascular stores in the body (adipose tissue complex).
      Technological advances in sterile, closed processing, has provided the ability to easily and
      safely acquire significant of stem/stromal cells for use in clinical studies.

      This study is aimed at evaluation of the safety profile (adverse reactions & severe adverse
      reactions) of the closed syringe, microcannula harvesting of subdermal fat deposits (largest
      known source of microvascular tissues in the body). This autologous cell group obtained with
      isolation and concentration of cells within the stromal vascular fraction (SVF) via enzymatic
      digestion, and deployed via intravascular r rebral fluids in defects of the blood brain
      barrier (BBB) or are small enough to pass into the fluids of the CNS (central nervous
      system). Effects are believed to be a function of both cellular multipotent abilities, but
      also regards the autocrine/paracrine secretory capacity of the cell group within the body.
      The body has the ability to request (chemotaxis) certain needed cellular and secreted
      chemicals to help healing and regeneration. Current thought are trending that the secretions
      may, in fact, be more important to the reparative and regenerative processes than the
      cellular contributions.

      In this study, disorders which involve autoimmune and inflammatory changes that impact the
      brain and nervous system are to be study, tracked and reported over time to determine
      ultimate efficacy and the "interval" therapy needs (or lack thereof) to maintain the
      accomplished arrest or improvement in the underlying tissues. Currently these intervals are
      examined by brain magnetic resonance imaging (MRI) with and without contrast. Correlation of
      image changes and clinical function will be made with subjective Quality of Life (Qol) and
      diary type observations by patients and caregivers.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participant with adverse events (AE) or severe adverse events (SAE)
time frame: 6 month intervals for up to 5 years
description: Activities of Daily Living (ADL)
measure: Neurological Function
time frame: 6 month Intervals for up to 5 years
description: Change from baseline of deficits of neurologic function identified by patient as impaired prior to study
measure: Neurological Tested Functions
time frame: 6 month interval for up to 5 years
description: Change from baseline of deficits of neurological function identified by medical provider as impaired prior to study
measure: Magnetic Resonance Imaging (MRI)
time frame: 6 month intervals for up to 5 years
description: Change in baseline of MRI with and without contrast at 6 month intervals
arm group label: Microcannula Harvest Adipose
arm group type: Experimental
description: Acquisition AD-tSVF Via Closed Syringe Microcannula
arm group label: Centricyte 1000
arm group type: Experimental
description: Autologous Adipose-Derived Tissue Stromal Vascular Fraction (tSVF) via enzymatic digestive isolation & concentration in Centricyte 1000 closed system to create AD-cSVF
arm group label: Sterile Normal Saline Infusion
arm group type: Experimental
description: Sterile Normal Saline to Re-Suspend Autologous cSVF pellet for delivery via intravascular (IV) route
intervention type: Procedure
intervention name: Microcannula Harvest Adipose
description: Use Closed Syringe Microcannula Harvest Adipose, Autologous Subdermal Deposits
arm group label: Microcannula Harvest Adipose
intervention type: Device
intervention name: Centricyte 1000
description: Closed System, Digestive Isolation & Concentration of AD-cSVF
arm group label: Centricyte 1000
intervention type: Procedure
intervention name: Sterile Normal Saline Infusion
description: Sterile Normal Saline Re-Suspension of cSVF and Delivery of AD-cSVF via IV route
arm group label: Sterile Normal Saline Infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Ryan Welter, MD, PhD
role: Principal Investigator
affiliation: Regeneris Medical Inc
last name: Glenn C Terry
role: Principal Investigator
affiliation: Global Alliance for Regenerative Medicine (GARM)
last name: Robert W Alexander, MD
role: Principal Investigator
affiliation: Healeon Medical
last name: Ryan Welter, MD, PhD
phone: 508.345.5492
email: r.welter@regenerismedical.com
last name: Kristin Corrado
phone: 508.316.4268
email: k.corrado@regenerismedical.com
facility: 
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
facility: 
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: United States
country: Honduras
citation: Litvan I, Agid Y, Goetz C, Jankovic J, Wenning GK, Brandel JP, Lai EC, Verny M, Ray-Chaudhuri K, McKee A, Jellinger K, Pearce RK, Bartko JJ. Accuracy of the clinical diagnosis of corticobasal degeneration: a clinicopathologic study. Neurology. 1997 Jan;48(1):119-25. doi: 10.1212/wnl.48.1.119.
PMID: 9008506
citation: Rizzo G, Martinelli P, Manners D, Scaglione C, Tonon C, Cortelli P, Malucelli E, Capellari S, Testa C, Parchi P, Montagna P, Barbiroli B, Lodi R. Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease. Brain. 2008 Oct;131(Pt 10):2690-700. doi: 10.1093/brain/awn195. Epub 2008 Sep 26.
PMID: 18819991
citation: Alladi S, Xuereb J, Bak T, Nestor P, Knibb J, Patterson K, Hodges JR. Focal cortical presentations of Alzheimer's disease. Brain. 2007 Oct;130(Pt 10):2636-45. doi: 10.1093/brain/awm213.
PMID: 17898010
citation: Sha SJ, Ghosh PM, Lee SE, Corbetta-Rastelli C, Jagust WJ, Kornak J, Rankin KP, Grinberg LT, Vinters HV, Mendez MF, Dickson DW, Seeley WW, Gorno-Tempini M, Kramer J, Miller BL, Boxer AL, Rabinovici GD. Predicting amyloid status in corticobasal syndrome using modified clinical criteria, magnetic resonance imaging and fluorodeoxyglucose positron emission tomography. Alzheimers Res Ther. 2015 Mar 2;7(1):8. doi: 10.1186/s13195-014-0093-y. eCollection 2015.
PMID: 25733984
citation: Jankovic J. Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):368-76. doi: 10.1136/jnnp.2007.131045.
PMID: 18344392
citation: Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry. 1988 Jun;51(6):745-52. doi: 10.1136/jnnp.51.6.745.
PMID: 2841426
citation: Pedrosa DJ, Timmermann L. Review: management of Parkinson's disease. Neuropsychiatr Dis Treat. 2013;9:321-40. doi: 10.2147/NDT.S32302. Epub 2013 Mar 3.
PMID: 23487540
citation: Mayo L, Quintana FJ, Weiner HL. The innate immune system in demyelinating disease. Immunol Rev. 2012 Jul;248(1):170-87. doi: 10.1111/j.1600-065X.2012.01135.x.
PMID: 22725961
citation: Ransohoff RM, Howe CL, Rodriguez M. Growth factor treatment of demyelinating disease: at last, a leap into the light. Trends Immunol. 2002 Nov;23(11):512-6. doi: 10.1016/s1471-4906(02)02321-9.
PMID: 12401395
responsible party type: Principal Investigator
investigator affiliation: Healeon Medical Inc
investigator full name: Ryan Welter, MD, PhD
investigator title: Principal Investigator, Science
mesh term: Alzheimer Disease
mesh term: Corticobasal Degeneration
mesh term: Demyelinating Autoimmune Diseases, CNS
mesh term: Autoimmune Diseases
sharing ipd: Undecided
ipd description: Annual Summary of Enrolled Cases By All collaborators, principle investigators, or accept sub-investigators