<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/NCT01716637</url>
  </required_header>
  <id_info>
    <org_study_id>CL025</org_study_id>
    <nct_id>NCT01716637</nct_id>
  </id_info>
  <brief_title>Short Term Efficacy and Safety of Perispinal Administration of Etanercept in Mild to Moderate Alzheimer's Disease</brief_title>
  <official_title>Open Label,Crossover,Pilot Study to Assess the Efficacy &amp; Safety of Perispinal Admin.of Etanercept(Enbrel®) in Comb.w/Nutritional Supplements vs. Nutritional Supplements Alone in Subj. w/Mild to Mod. Alzheimer's Disease Receiving Std. Care.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Life Extension Foundation Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Life Extension Foundation Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      While the cause of AD is still unknown, evidence suggests it develops because of a complex&#xD;
      series of events in the brain that occur over time. Two pathways possibly involved in&#xD;
      development of AD are inflammation and oxidative stress. Scientists have linked chronic&#xD;
      inflammatory events in the brain with the onset and progression of Alzheimer's Disease.&#xD;
      Oxidative stress has also been implicated in the pathogenesis of a number of neurological&#xD;
      disorders including Alzheimer's Disease.&#xD;
&#xD;
      Etanercept (Enbrel®) is an approved drug for the treatment of several forms of arthritis when&#xD;
      administered by injection. Some research suggests that etanercept, when administered by&#xD;
      injection into the tissues close to the spinal column (perispinally), may modulate certain&#xD;
      aspects of the immune system and provide some beneficial effect for people with Alzheimer's&#xD;
      disease. Studies suggest that supplementation with specific nutrients may also have a&#xD;
      positive effect in support of cognitive function.&#xD;
&#xD;
      This study will be conducted at one research office with volunteers who have been diagnosed&#xD;
      with mild to moderate Alzheimer's disease. Each qualifying participant will be randomly&#xD;
      assigned to receive an etanercept injection plus nutritional supplements for 6 weeks followed&#xD;
      by a crossover and a washout period of 4 weeks to then receiving nutritional supplements&#xD;
      alone or vice versa for another 6 weeks.&#xD;
&#xD;
      Participants will undergo blood and urine safety assessments at the beginning and end of each&#xD;
      6 week treatment period. During 4 of the 6 weekly visits in the treatment period with the&#xD;
      injections, you will complete the cognitive tests twice; once before and once 2 hours after&#xD;
      the injection. During 4 of the 6 weekly visits in the treatment period without the&#xD;
      injections, you will also complete the cognitive tests twice; once before and once 2 hours&#xD;
      after being asked to lie down onto a table for 5 minutes. You will be allowed to continue&#xD;
      your standard of care for Alzheimer's disease throughout your participation in the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2010</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">October 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Mini-Mental Status Examination (MMSE) score.</measure>
    <time_frame>16 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) score.</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Montreal Cognitive Assessment (MoCA) score.</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the MMSE score.</measure>
    <time_frame>28 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Difference in short term effects of etanercept on the MMSE score before and two hours after perispinal administration of etanercept.</measure>
    <time_frame>16 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>To determine the safety and tolerability of nutritional supplements with perispinal adminstration of etanercept, as measured by various laboratory markers, vital signs (blood pressure and heart rate), and adverse events.</measure>
    <time_frame>16 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the ADAS-cog score.</measure>
    <time_frame>28 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the MoCA score.</measure>
    <time_frame>28 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Difference in short term effects of etanercept on the ADAS-cog score before and two hours after perispinal administration of etanercept.</measure>
    <time_frame>16 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Difference in short term effects of etanercept on the MoCA score before and two hours after perispinal administration of etanercept.</measure>
    <time_frame>16 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>To determine the safety and tolerability of nutritional supplements without perispinal adminstration of etanercept, as measured by various laboratory markers, vital signs (blood pressure and heart rate), and adverse events.</measure>
    <time_frame>16 weeks</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>Etanercept</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>25 mg administered weekly for 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nutritional Supplements</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Nutritional supplements administered daily for 6 weeks in each period as well as an additional 12 weeks following visit 15.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Etanercept</intervention_name>
    <arm_group_label>Etanercept</arm_group_label>
    <other_name>Enbrel®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr.</intervention_name>
    <arm_group_label>Etanercept</arm_group_label>
    <arm_group_label>Nutritional Supplements</arm_group_label>
    <other_name>Super Bio-Curcumin</other_name>
    <other_name>Super Omega-3</other_name>
    <other_name>Optimized Quercetin</other_name>
    <other_name>Optimized Resveratrol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject is aged 60-85 years&#xD;
&#xD;
          -  Subject has a diagnosis of Alzheimer's disease according to the NINCDS- ADRDA criteria&#xD;
             (National Institute of Neurological and Communicative Disorders and Stroke NINCDS] and&#xD;
             Alzheimer's Disease and Related Disorders Association [ADRDA]).&#xD;
&#xD;
          -  Subject is not institutionalized (for example, lives independently, lives&#xD;
             independently in a residential home for the elderly, or is a day patient at a care&#xD;
             center)&#xD;
&#xD;
          -  Subject has a Hachinski Ischemia Score of ≤ 4.&#xD;
&#xD;
          -  Subject has a total MoCA score of &lt; 26 at screening.&#xD;
&#xD;
          -  Subject has an MMSE score of 11 to 24 at screening.&#xD;
&#xD;
          -  Subject has an ADAS-cog score of 12 to 25 at screening.&#xD;
&#xD;
          -  Subject has experienced a gradual and progressive cognitive decline in the 6 months&#xD;
             before the screening visit.&#xD;
&#xD;
          -  Subject provides informed consent to participate in the study or has a legally&#xD;
             acceptable representative who provides consent.&#xD;
&#xD;
          -  Subject has a responsible caregiver who consents to supporting the subject in his/her&#xD;
             study participation (for example, by accompanying the subject on each study visit).&#xD;
&#xD;
          -  Subject is surgically sterile, agrees to use an acceptable method of birth control as&#xD;
             defined in section 5.4 or, for females, is post- menopausal.&#xD;
&#xD;
          -  Subject agrees to stop taking any vitamin, mineral, or dietary supplements he/she is&#xD;
             currently taking that have any components of the nutritional supplements utilized in&#xD;
             the study at least 7 days before randomization (Visit 2) and agrees to not use any new&#xD;
             vitamin, mineral, or dietary supplement product other than those provided by the&#xD;
             investigator until after the subject is discharged from the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A neurologic disorder, such as seizures, multiple sclerosis, neurodegenerative&#xD;
             disorders (eg, Parkinson's disease), or dementia other than Alzheimer's type&#xD;
             (including that caused by small strokes or cerebrovascular disease)&#xD;
&#xD;
          -  Cognitive impairment from any condition other than Alzheimer's disease, such as that&#xD;
             resulting from acute cerebral trauma, cerebral damage due to a lack of oxygen,&#xD;
             infections such as meningitis or AIDS, significant endocrine or metabolic disease,&#xD;
             mental retardation, or a brain tumor&#xD;
&#xD;
          -  Cardiovascular or cerebrovascular disease, such as congestive heart failure,&#xD;
             uncontrolled hypertension (BP ≥ 140/90 mmHg at screening), and a history of stroke&#xD;
&#xD;
          -  Renal impairment/disease, defined as serum creatinine &gt; 1.5 mg/dL&#xD;
&#xD;
          -  Hepatic impairment, defined as Alanine Aminotransferase (ALT) or Aspartate&#xD;
             Aminotransferase (AST) &gt; 3 times the upper limit of normal OR has a history of a&#xD;
             positive blood screen for hepatitis B surface antigen or hepatitis C antibody.&#xD;
&#xD;
          -  Type I or II diabetes mellitus&#xD;
&#xD;
          -  Significant or uncontrolled psychiatric disease&#xD;
&#xD;
          -  Gastrointestinal disease, such as active peptic ulcer, gallstones, gallbladder&#xD;
             disease, or biliary tract obstruction, or a history of cholecystectomy&#xD;
&#xD;
          -  Hematologic disorders&#xD;
&#xD;
          -  Pulmonary or lung disorders&#xD;
&#xD;
          -  Immune system disorder, such as HIV/AIDS&#xD;
&#xD;
          -  History of cancer within 10 years before screening (except localized skin cancer&#xD;
             without metastases or in situ cervical cancer)&#xD;
&#xD;
          -  History of chronic or recurrent infection (including tuberculosis) OR, in the 7 days&#xD;
             before Visit 2 (randomization), any known infection or body temperature &gt; 38.6º C&#xD;
             (101.5º F)&#xD;
&#xD;
          -  Subject is pregnant or breastfeeding at screening.&#xD;
&#xD;
          -  Subject has intolerance or allergy to Enbrel®, latex, or any of Enbrel's components.&#xD;
&#xD;
          -  Subject is currently consuming more than 6 standard alcoholic beverages a week. A&#xD;
             standard alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine, or 1.5&#xD;
             ounces of liquor.&#xD;
&#xD;
          -  Subject is currently taking and unable or unwilling to stop taking anticoagulant or&#xD;
             antiplatelet herbs and supplements such as angelica, clove, danshen, garlic, ginger,&#xD;
             ginkgo, Panax ginseng, red clover, or willow for at least 7 days before the&#xD;
             randomization visit (Visit 2) and throughout the study.&#xD;
&#xD;
          -  Subject is currently taking and unable or unwilling to stop taking any of the&#xD;
             prohibited medications in protocol section 5.3.2 for at least 7 days before the&#xD;
             randomization visit (Visit 2) and throughout the study.&#xD;
&#xD;
          -  Subject had major surgery within the 4 weeks before screening.&#xD;
&#xD;
          -  Subject has any condition or abnormality that, in the opinion of the investigator,&#xD;
             would compromise the safety of the subject or the quality of the study data.&#xD;
&#xD;
          -  Subject is participating or has participated in another research study within 30 days&#xD;
             before the screening visit&#xD;
&#xD;
          -  Subject or subject's caregiver is unable or unwilling to comply with the study&#xD;
             procedures.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul H. Wand, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Paul H. Wand M.D., P.A.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mark L. Brody, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brain Matters Research Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Paul H. Wand M.D., P.A.</name>
      <address>
        <city>Coral Springs</city>
        <state>Florida</state>
        <zip>33065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Matters Research</name>
      <address>
        <city>Delray Beach</city>
        <state>Florida</state>
        <zip>33445</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
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    <citation>Freund-Levi Y, Eriksdotter-Jonhagen M, Cederholm T, Basun H, Faxen-Irving G, Garlind A, Vedin I, Vessby B, Wahlund LO, Palmblad J. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial. Arch Neurol. 2006 Oct;63(10):1402-8. doi: 10.1001/archneur.63.10.1402.</citation>
    <PMID>17030655</PMID>
  </reference>
  <reference>
    <citation>Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol. 1980 May;7(5):486-8. doi: 10.1002/ana.410070516.</citation>
    <PMID>7396427</PMID>
  </reference>
  <verification_date>May 2016</verification_date>
  <study_first_submitted>October 5, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 30, 2012</study_first_posted>
  <last_update_submitted>May 10, 2016</last_update_submitted>
  <last_update_submitted_qc>May 10, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alzheimer's Disease</keyword>
  <keyword>Dementia</keyword>
  <keyword>Cognitive decline</keyword>
  <keyword>Cognitive disorder</keyword>
  <keyword>Degenerative brain disease</keyword>
  <keyword>Cognitive impairment</keyword>
  <keyword>Memory loss</keyword>
  <keyword>TNF-alpha</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Etanercept</mesh_term>
    <mesh_term>Curcumin</mesh_term>
    <mesh_term>Resveratrol</mesh_term>
    <mesh_term>Quercetin</mesh_term>
  </intervention_browse>
  <!-- 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/NCT01716637
org study id: CL025
nct id: NCT01716637
lead sponsor: 
has dmc: No
While the cause of AD is still unknown, evidence suggests it develops because of a complex
      series of events in the brain that occur over time. Two pathways possibly involved in
      development of AD are inflammation and oxidative stress. Scientists have linked chronic
      inflammatory events in the brain with the onset and progression of Alzheimer's Disease.
      Oxidative stress has also been implicated in the pathogenesis of a number of neurological
      disorders including Alzheimer's Disease.

      Etanercept (Enbrel®) is an approved drug for the treatment of several forms of arthritis when
      administered by injection. Some research suggests that etanercept, when administered by
      injection into the tissues close to the spinal column (perispinally), may modulate certain
      aspects of the immune system and provide some beneficial effect for people with Alzheimer's
      disease. Studies suggest that supplementation with specific nutrients may also have a
      positive effect in support of cognitive function.

      This study will be conducted at one research office with volunteers who have been diagnosed
      with mild to moderate Alzheimer's disease. Each qualifying participant will be randomly
      assigned to receive an etanercept injection plus nutritional supplements for 6 weeks followed
      by a crossover and a washout period of 4 weeks to then receiving nutritional supplements
      alone or vice versa for another 6 weeks.

      Participants will undergo blood and urine safety assessments at the beginning and end of each
      6 week treatment period. During 4 of the 6 weekly visits in the treatment period with the
      injections, you will complete the cognitive tests twice; once before and once 2 hours after
      the injection. During 4 of the 6 weekly visits in the treatment period without the
      injections, you will also complete the cognitive tests twice; once before and once 2 hours
      after being asked to lie down onto a table for 5 minutes. You will be allowed to continue
      your standard of care for Alzheimer's disease throughout your participation in the study.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Health Services Research
masking: None (Open Label)
measure: Difference in effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Mini-Mental Status Examination (MMSE) score.
time frame: 16 weeks
measure: Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) score.
time frame: 16 weeks
measure: Difference in the effects of treatment for 6 weeks with etanercept + nutritional supplements versus nutritional supplements alone on the Montreal Cognitive Assessment (MoCA) score.
time frame: 16 weeks
measure: Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the MMSE score.
time frame: 28 weeks
measure: Difference in short term effects of etanercept on the MMSE score before and two hours after perispinal administration of etanercept.
time frame: 16 weeks
measure: To determine the safety and tolerability of nutritional supplements with perispinal adminstration of etanercept, as measured by various laboratory markers, vital signs (blood pressure and heart rate), and adverse events.
time frame: 16 weeks
measure: Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the ADAS-cog score.
time frame: 28 weeks
measure: Difference in the effects of treatment for 6 weeks as well as an additional 12 weeks following visit 15 with nutritional supplementation alone on the MoCA score.
time frame: 28 weeks
measure: Difference in short term effects of etanercept on the ADAS-cog score before and two hours after perispinal administration of etanercept.
time frame: 16 weeks
measure: Difference in short term effects of etanercept on the MoCA score before and two hours after perispinal administration of etanercept.
time frame: 16 weeks
measure: To determine the safety and tolerability of nutritional supplements without perispinal adminstration of etanercept, as measured by various laboratory markers, vital signs (blood pressure and heart rate), and adverse events.
time frame: 16 weeks
arm group label: Etanercept
arm group type: Active Comparator
description: 25 mg administered weekly for 6 weeks
arm group label: Nutritional Supplements
arm group type: Active Comparator
description: Nutritional supplements administered daily for 6 weeks in each period as well as an additional 12 weeks following visit 15.
intervention type: Biological
intervention name: Etanercept
arm group label: Etanercept
other name: Enbrel®
intervention type: Dietary Supplement
intervention name: Curcum.Luteol.Theaflav.Lip.Acid,FishOil,Quercet.,Resveratr.
arm group label: Etanercept
arm group label: Nutritional Supplements
other name: Super Bio-Curcumin
other name: Super Omega-3
other name: Optimized Quercetin
other name: Optimized Resveratrol
criteria: 
gender: All
minimum age: 60 Years
maximum age: 85 Years
healthy volunteers: No
last name: Paul H. Wand, M.D.
role: Principal Investigator
affiliation: Paul H. Wand M.D., P.A.
last name: Mark L. Brody, M.D.
role: Principal Investigator
affiliation: Brain Matters Research Inc.
facility: 
facility: 
country: United States
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PMID: 17030655
citation: Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A. Pathological verification of ischemic score in differentiation of dementias. Ann Neurol. 1980 May;7(5):486-8. doi: 10.1002/ana.410070516.
PMID: 7396427
responsible party type: Sponsor
mesh term: Alzheimer Disease
mesh term: Etanercept
mesh term: Curcumin
mesh term: Resveratrol
mesh term: Quercetin