xml: <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/NCT06019117</url>
    </required_header>
    <id_info>
      <org_study_id>2023001</org_study_id>
      <secondary_id>13536327</secondary_id>
      <nct_id>NCT06019117</nct_id>
    </id_info>
    <brief_title>Effectiveness of Probiotic K10 in Managing Health Outcomes in Parkinson and Alzheimer Disease</brief_title>
    <acronym>Probiótic</acronym>
    <official_title>Effectiveness of a Probiotic K10 in Managing Health Outcomes in Parkinson's Disease and in Early Stage (Mild Cognitive Impairment to Mild Dementia) Alzheimer's Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Deivis de Oliveira guimaraes</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Gon1 Gestao de Projetos</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Evaluation of the effects of the K10 probiotic mix in patients with degenerative neurological&#xD;
        diseases (Parkinson and Alzheimer's) with a focus on cognitive, motor and psychiatric&#xD;
        neurological evaluation.&#xD;
  &#xD;
        Single-centre, double-blind, placebo-controlled randomized clinical trial (RCT),&#xD;
        Interventional Model: Parallel Assignment, phase III study. Two groups will be composed, with&#xD;
        two arms each, 1 group composed of patients with Parkinson's and 1 group with patients with&#xD;
        Alzheimer's, 52 patients in each group. The first arm of each group will receive placebo and&#xD;
        the other arm of each group will receive the mix K10.&#xD;
  &#xD;
        In this study, researchers will conduct a randomized, placebo-controlled, phase III trial of&#xD;
        a probiotic preparation (Probiotic K10) to evaluate its use as a viable treatment option for&#xD;
        neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease. of&#xD;
        Alzheimer (AD). This formulation has been previously demonstrated to improve cognitive&#xD;
        function, systemic inflammation, systemic oxidative stress in Alzheimer's patients. The main&#xD;
        objective of this study is to compare its effect with placebo on cognitive status in&#xD;
        individuals with AD and PD, the UPDRS total score in people with early PD and quality of&#xD;
        life, and the measurement of caregiver burden in AD and PD. Participants will be randomly&#xD;
        assigned to receive a placebo (an inactive substance) and a K10 probiotic (dose 2 ml/kg/day).&#xD;
        They will be evaluated at baseline, 45 days and 90 days.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Change in urinary cortisol dosage Determination of cortisol levels can be used as an indirect&#xD;
        measurement of emotional stress. Reduced levels of this hormone are related to reduced&#xD;
        cardiovascular risk and reduced inflammatory damage.&#xD;
  &#xD;
        Baseline to T90 or the time of sufficient disability to study closure.&#xD;
  &#xD;
        All measurements will be taken at time zero (start of the survey), the next measurement in 45&#xD;
        days and the last measurement in 90 days. We will use the comparison of the data collected&#xD;
        from each individual at time zero in comparison with their own results collected at the next&#xD;
        times, using biostatistics to compare the results and, at the end of the primary result, we&#xD;
        will perform the simple tabulation to count the values of each analyzed variable.&#xD;
  &#xD;
        Differences between measures of central tendency with pr &lt; 0.05 will be considered&#xD;
        statistically significant. When the central tendency values present a normal distribution in&#xD;
        the statistical test, a parametric test will be used. In the case of comparison of 2 means,&#xD;
        Student's t test will be used, for paired or independent samples. When the comparison&#xD;
        includes more than 2 means, analysis of variance (ANOVA) will be used for 1 way (a single&#xD;
        factor, e.g. treatment time) or 2 ways (two factors, for example treatment time and control&#xD;
        group x treated group ).&#xD;
  &#xD;
        After verifying a significant difference in ANOVA, a post hoc protected t-test will then be&#xD;
        applied to detect at which points in the analysis there are pairs with significant&#xD;
        differences. When the analysis of the distribution (frequency) of the data shows a&#xD;
        distribution that is not compatible with the Gaussian distribution, a corresponding&#xD;
        non-parametric test will be used. Contingency tables 2 x 2 will also be used for later&#xD;
        calculation of risk factors and to determine the significance through the X2 test.&#xD;
  &#xD;
        The software to be used will be Prism from Graphpad v. 9&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">August 10, 2023</start_date>
    <completion_date type="Anticipated">December 20, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 11, 2023</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Single-centre, double-blind, placebo-controlled randomized clinical trial (RCT), Interventional Model: Parallel Assignment, phase III study.</intervention_model_description>
      <primary_purpose>Supportive Care</primary_purpose>
      <masking>Single (Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in MDS-Unified (PD)</measure>
      <time_frame>1st, 45 and 90 days</time_frame>
      <description>scale (MDS- UPDRS) the sum of parts I, II and III ranges from 0 to 176. The MDS-UPDRS score has three components, each consisting of questions with 0-4 point scale. Part I assesses mentation, behavior, and mood; Part II assesses activities of daily; and Part III assesses motor abilities. Where 0 represents the absence of impairment and 4 represents the highest degree of impairment.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in quality of life scale (PD)</measure>
      <time_frame>1st, 45 and 90 days</time_frame>
      <description>Questionnaire (PDQ-39) that will evaluate their health and overall quality of life. The total of 39 aspects of quality of life, maximum score is 132. Each aspect is rated on scale of 0 (best outcome) to 4 (worst outcome). A higher score or increased score compared to a previous visit indicates a lowered quality of life.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes in anxiety levels (PD&amp;AD)</measure>
      <time_frame>1st, 45 and 90 days</time_frame>
      <description>Changes in anxiety levels, mood improvement and caregiver burden will be determined by applying the Neuropsychiatric Questionnaire (NPI-Q)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes in cognitive status measured by brief battery (AD)</measure>
      <time_frame>1st, 45 and 90 days</time_frame>
      <description>Mini Mental State Examination (MMSE): maximum score 30 points. Higher values indicate greater cognitive performance.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Quality of Life (QOL) (AD)</measure>
      <time_frame>1st, 45 and 90 days</time_frame>
      <description>13-item QOL-AD scale (total score range 13-52; higher scores indicate better QOL). The QOL-AD scale uses 1-4 (poor, fair, good, or excellent) to rate a variety of life domains, including the patient's physical health, mood, relationships, activities, and ability to complete tasks.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in cortisol dosage (Parkinson's and Alzheimer's group)</measure>
      <time_frame>1st, 45 and 90 days</time_frame>
      <description>Determination of cortisol levels can be used as an indirect measurement of emotional stress. Reduced levels of this hormone are related to reduced cardiovascular risk and reduced inflammatory damage.</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">104</enrollment>
    <condition>Parkinson Disease</condition>
    <condition>Alzheimer Disease</condition>
    <arm_group>
      <arm_group_label>Arm 1 - volunteers with parkinson's disease</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>26 patients in this arm. in this arm will receive the probiotic K10 (2mg/kg/dia).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm 2 - volunteers with parkinson's disease</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>26 patients in this arm. In this arm will receive the controlled placebo.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm 3- volunteers with alzheimer's disease</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>26 patients in this arm. in this arm will receive the probiotic K10 (2mg/kg/dia).</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm 4- volunteers with alzheimer's disease</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>26 patients in this arm. In this arm will receive the controlled placebo.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Probiotic K10</intervention_name>
      <description>clinical trial using 90 days of probiotic K10</description>
      <arm_group_label>Arm 1 - volunteers with parkinson's disease</arm_group_label>
      <arm_group_label>Arm 3- volunteers with alzheimer's disease</arm_group_label>
      <other_name>Cerenovex</other_name>
      <other_name>Neurobiotic</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>clinical trial using 90 days of placebo controlled</description>
      <arm_group_label>Arm 2 - volunteers with parkinson's disease</arm_group_label>
      <arm_group_label>Arm 4- volunteers with alzheimer's disease</arm_group_label>
      <other_name>flour</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Eligibility criteria for individuals with Parkinson's. Ages eligible to participate in the&#xD;
          study: 18 years or older Accept healthy volunteers: No. Gender Eligibility for Study: All&#xD;
          genders&#xD;
  &#xD;
          Inclusion criteria:&#xD;
  &#xD;
            -  Presence of all 3 cardinal features of Parkinson's disease (tooth tremor,&#xD;
               bradykinesia, and rigidity). Clinical signs must be asymmetrical.&#xD;
  &#xD;
            -  Diagnosis of Parkinson's disease within 5 years of the Screening Visit.&#xD;
  &#xD;
            -  Age 18 years or older.&#xD;
  &#xD;
            -  Women must not be of childbearing potential or must use an approved form of&#xD;
               contraception during the trial period.&#xD;
  &#xD;
          Eligibility Criteria for Individuals with Alzheimer's. Eligible ages to participate in the&#xD;
          study: 60 -85 years Accept healthy volunteers: No. Gender Eligibility for Study: All&#xD;
          genders&#xD;
  &#xD;
          Inclusion criteria:&#xD;
  &#xD;
            -  Men or women between the ages of 60 and 85&#xD;
  &#xD;
            -  Diagnosis of probable Alzheimer's disease&#xD;
  &#xD;
            -  Portuguese-speaking, English-speaking; Spanish-speaking if the individual site allows&#xD;
  &#xD;
            -  Study partner or caregiver to ensure compliance&#xD;
  &#xD;
            -  Mini-Mental State Exam score at screening visit greater than 14&#xD;
  &#xD;
            -  Stable medical condition for 3 months prior to screening, with no significant abnormal&#xD;
               liver, kidney, or blood studies.&#xD;
  &#xD;
            -  Able to take oral medications&#xD;
  &#xD;
            -  Modified Hachinski Ischemic Index less than or equal to 4&#xD;
  &#xD;
            -  CT or MRI from the onset of memory impairment, demonstrating the absence of a&#xD;
               clinically significant focal lesion&#xD;
  &#xD;
            -  Physically acceptable for this study, as confirmed by medical history, physical&#xD;
               examination, neurological examination, and clinical testing&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          Parkinson's Exclusion Criteria:&#xD;
  &#xD;
            -  Parkinsonism due to drugs including neuroleptics, alpha-methyldopa, reserpine,&#xD;
               metoclopramide, valproic acid.&#xD;
  &#xD;
            -  Use of antioxidants (such as selegiline, rasagiline, vitamins E and C), additional&#xD;
               supplemental vitamins or minerals, regular use of neuroleptics, chloramphenicol,&#xD;
               valproic acid, warfarin.&#xD;
  &#xD;
            -  Other parkinsonian disorders.&#xD;
  &#xD;
            -  Modified Hoehn and Yahr score of 3 or more on Screening Visit or Baseline Visit.&#xD;
  &#xD;
            -  UPDRS tremor score of 3 or greater at Screening Visit or Baseline Visit.&#xD;
  &#xD;
            -  History of symptomatic stroke.&#xD;
  &#xD;
            -  Sufficient deficiency to require changes in dopaminergic medication treatment during&#xD;
               follow-up compared to baseline treatment schedule.&#xD;
  &#xD;
            -  Other severe and uncompensated illnesses, including severe psychiatric illnesses.&#xD;
  &#xD;
            -  Patients with active cardiovascular, restrictive peripheral vascular, or&#xD;
               cerebrovascular disease in the past year.&#xD;
  &#xD;
            -  Unstable dose of active CNS therapies.&#xD;
  &#xD;
            -  Use of appetite suppressants within 60 days of the Baseline Visit.&#xD;
  &#xD;
            -  History of active epilepsy within the past 5 years.&#xD;
  &#xD;
            -  Participation in other drug studies or use of other investigational drugs within 30&#xD;
               days prior to the Screening Visit.&#xD;
  &#xD;
            -  History of electroconvulsive therapy.&#xD;
  &#xD;
            -  History of any brain surgery for Parkinson's disease.&#xD;
  &#xD;
            -  History of structural brain disease, such as previous trauma causing damage detected&#xD;
               on a CT scan or MRI, hydrocephalus, or previous brain neoplasms.&#xD;
  &#xD;
          Alzheimer's Exclusion Criteria:&#xD;
  &#xD;
            -  Significant neurological disease such as Parkinson's disease, stroke, brain tumor,&#xD;
               multiple sclerosis, or seizure disorder&#xD;
  &#xD;
            -  Major depression treated in the past 12 months, major mental illness such as&#xD;
               schizophrenia, or recent (in past 12 months) alcohol or substance abuse&#xD;
  &#xD;
            -  History of invasive cancer within the past two years (excluding non-melanoma skin&#xD;
               cancer)&#xD;
  &#xD;
            -  Use of any investigational agents within 30 days prior to screening&#xD;
  &#xD;
            -  Major surgery within 8 weeks prior to the Baseline Visit&#xD;
  &#xD;
            -  Uncontrolled cardiac conditions or severe unstable medical illnesses&#xD;
  &#xD;
            -  Antiretroviral therapy for human immunodeficiency virus (HIV)&#xD;
  &#xD;
            -  Conditions that will contribute to oxidative stress: current cigarette or cigar&#xD;
               smokers (within past month), diabetics on insulin or poorly controlled on oral&#xD;
               hypoglycemics&#xD;
  &#xD;
            -  Blindness, deafness, language difficulties or any other disability which may prevent&#xD;
               the participant from participating or cooperating in the protocol.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <gender_based>Yes</gender_based>
      <gender_description>Parkinson under 18 years. Alzheimer between 60 and 85 years</gender_description>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Alyne M Ton, post-doc</last_name>
      <role>Principal Investigator</role>
      <affiliation>Gon1 Gestora de Projetos</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Roberto S Badaró, post-doc</last_name>
      <role>Study Director</role>
      <affiliation>SENAI CIMATEC</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Gon1 gestora de Projetos</name>
        <address>
          <city>Vitória</city>
          <state>ES</state>
          <zip>29050335</zip>
          <country>Brazil</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Brazil</country>
    </location_countries>
    <reference>
      <citation>Mazloom Z, Yousefinejad A, Dabbaghmanesh MH. Effect of probiotics on lipid profile, glycemic control, insulin action, oxidative stress, and inflammatory markers in patients with type 2 diabetes: a clinical trial. Iran J Med Sci. 2013 Mar;38(1):38-43.</citation>
      <PMID>23645956</PMID>
    </reference>
    <reference>
      <citation>Liu Z, Li T, Li P, Wei N, Zhao Z, Liang H, Ji X, Chen W, Xue M, Wei J. The Ambiguous Relationship of Oxidative Stress, Tau Hyperphosphorylation, and Autophagy Dysfunction in Alzheimer's Disease. Oxid Med Cell Longev. 2015;2015:352723. doi: 10.1155/2015/352723. Epub 2015 Jun 15.</citation>
      <PMID>26171115</PMID>
    </reference>
    <reference>
      <citation>Mishra V, Shah C, Mokashe N, Chavan R, Yadav H, Prajapati J. Probiotics as potential antioxidants: a systematic review. J Agric Food Chem. 2015 Apr 15;63(14):3615-26. doi: 10.1021/jf506326t. Epub 2015 Apr 6.</citation>
      <PMID>25808285</PMID>
    </reference>
    <reference>
      <citation>Licker V, Kovari E, Hochstrasser DF, Burkhard PR. Proteomics in human Parkinson's disease research. J Proteomics. 2009 Nov 2;73(1):10-29. doi: 10.1016/j.jprot.2009.07.007. Epub 2009 Jul 24.</citation>
      <PMID>19632367</PMID>
    </reference>
    <reference>
      <citation>Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, &quot;prefrontal&quot; and &quot;limbic&quot; functions. Prog Brain Res. 1990;85:119-46.</citation>
      <PMID>2094891</PMID>
    </reference>
    <reference>
      <citation>Obeso JA, Rodriguez-Oroz MC, Chana P, Lera G, Rodriguez M, Olanow CW. The evolution and origin of motor complications in Parkinson's disease. Neurology. 2000;55(11 Suppl 4):S13-20; discussion S21-3.</citation>
      <PMID>11147505</PMID>
    </reference>
    <reference>
      <citation>Sood B, Keenaghan M. Coenzyme Q10. 2022 Jan 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK531491/</citation>
      <PMID>30285386</PMID>
    </reference>
    <reference>
      <citation>Arenas-Jal M, Sune-Negre JM, Garcia-Montoya E. Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges. Compr Rev Food Sci Food Saf. 2020 Mar;19(2):574-594. doi: 10.1111/1541-4337.12539. Epub 2020 Feb 19.</citation>
      <PMID>33325173</PMID>
    </reference>
    <reference>
      <citation>Garrido-Maraver J, Cordero MD, Oropesa-Avila M, Vega AF, de la Mata M, Pavon AD, Alcocer-Gomez E, Calero CP, Paz MV, Alanis M, de Lavera I, Cotan D, Sanchez-Alcazar JA. Clinical applications of coenzyme Q10. Front Biosci (Landmark Ed). 2014 Jan 1;19(4):619-33. doi: 10.2741/4231.</citation>
      <PMID>24389208</PMID>
    </reference>
    <results_reference>
      <citation>Valentini L, Pinto A, Bourdel-Marchasson I, Ostan R, Brigidi P, Turroni S, Hrelia S, Hrelia P, Bereswill S, Fischer A, Leoncini E, Malaguti M, Blanc-Bisson C, Durrieu J, Spazzafumo L, Buccolini F, Pryen F, Donini LM, Franceschi C, Lochs H. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The &quot;RISTOMED project&quot;: Randomized controlled trial in healthy older people. Clin Nutr. 2015 Aug;34(4):593-602. doi: 10.1016/j.clnu.2014.09.023. Epub 2014 Oct 8.</citation>
      <PMID>25453395</PMID>
    </results_reference>
    <results_reference>
      <citation>Padurariu M, Ciobica A, Lefter R, Serban IL, Stefanescu C, Chirita R. The oxidative stress hypothesis in Alzheimer's disease. Psychiatr Danub. 2013 Dec;25(4):401-9.</citation>
      <PMID>24247053</PMID>
    </results_reference>
    <results_reference>
      <citation>Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog Neurobiol. 2001 Oct;65(2):135-72. doi: 10.1016/s0301-0082(01)00003-x.</citation>
      <PMID>11403877</PMID>
    </results_reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 31, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 31, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Gon1 Gestao de Projetos</investigator_affiliation>
      <investigator_full_name>Deivis de Oliveira guimaraes</investigator_full_name>
      <investigator_title>CRO general manager</investigator_title>
    </responsible_party>
    <keyword>Probiotic</keyword>
    <keyword>Alzheimer</keyword>
    <keyword>Parkinson</keyword>
    <keyword>Neurological desease</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Parkinson Disease</mesh_term>
      <mesh_term>Alzheimer Disease</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>We can share all data regarding data collection, preserving the personal data of volunteers and as long as the request does not go beyond the limits of confidentiality, integrity and ethics.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>They will be available after data collection and analysis, and will be abble for 1 year after the trial end.</ipd_time_frame>
      <ipd_access_criteria>will be available upon request and for exclusive access to scientists, governmental and scientific organizations.</ipd_access_criteria>
      <ipd_url>http://www.gon1.com.br/ipd</ipd_url>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Informed Consent Form</document_type>
        <document_has_protocol>No</document_has_protocol>
        <document_has_icf>Yes</document_has_icf>
        <document_has_sap>No</document_has_sap>
        <document_date>August 18, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT06019117/ICF_000.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06019117
  org study id: 2023001
  secondary id: 13536327
  nct id: NCT06019117
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Evaluation of the effects of the K10 probiotic mix in patients with degenerative neurological
        diseases (Parkinson and Alzheimer's) with a focus on cognitive, motor and psychiatric
        neurological evaluation.
  
        Single-centre, double-blind, placebo-controlled randomized clinical trial (RCT),
        Interventional Model: Parallel Assignment, phase III study. Two groups will be composed, with
        two arms each, 1 group composed of patients with Parkinson's and 1 group with patients with
        Alzheimer's, 52 patients in each group. The first arm of each group will receive placebo and
        the other arm of each group will receive the mix K10.
  
        In this study, researchers will conduct a randomized, placebo-controlled, phase III trial of
        a probiotic preparation (Probiotic K10) to evaluate its use as a viable treatment option for
        neurodegenerative disorders, including Parkinson's disease (PD) and Alzheimer's disease. of
        Alzheimer (AD). This formulation has been previously demonstrated to improve cognitive
        function, systemic inflammation, systemic oxidative stress in Alzheimer's patients. The main
        objective of this study is to compare its effect with placebo on cognitive status in
        individuals with AD and PD, the UPDRS total score in people with early PD and quality of
        life, and the measurement of caregiver burden in AD and PD. Participants will be randomly
        assigned to receive a placebo (an inactive substance) and a K10 probiotic (dose 2 ml/kg/day).
        They will be evaluated at baseline, 45 days and 90 days.
  Change in urinary cortisol dosage Determination of cortisol levels can be used as an indirect
        measurement of emotional stress. Reduced levels of this hormone are related to reduced
        cardiovascular risk and reduced inflammatory damage.
  
        Baseline to T90 or the time of sufficient disability to study closure.
  
        All measurements will be taken at time zero (start of the survey), the next measurement in 45
        days and the last measurement in 90 days. We will use the comparison of the data collected
        from each individual at time zero in comparison with their own results collected at the next
        times, using biostatistics to compare the results and, at the end of the primary result, we
        will perform the simple tabulation to count the values of each analyzed variable.
  
        Differences between measures of central tendency with pr < 0.05 will be considered
        statistically significant. When the central tendency values present a normal distribution in
        the statistical test, a parametric test will be used. In the case of comparison of 2 means,
        Student's t test will be used, for paired or independent samples. When the comparison
        includes more than 2 means, analysis of variance (ANOVA) will be used for 1 way (a single
        factor, e.g. treatment time) or 2 ways (two factors, for example treatment time and control
        group x treated group ).
  
        After verifying a significant difference in ANOVA, a post hoc protected t-test will then be
        applied to detect at which points in the analysis there are pairs with significant
        differences. When the analysis of the distribution (frequency) of the data shows a
        distribution that is not compatible with the Gaussian distribution, a corresponding
        non-parametric test will be used. Contingency tables 2 x 2 will also be used for later
        calculation of risk factors and to determine the significance through the X2 test.
  
        The software to be used will be Prism from Graphpad v. 9
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Single-centre, double-blind, placebo-controlled randomized clinical trial (RCT), Interventional Model: Parallel Assignment, phase III study.
  primary purpose: Supportive Care
  masking: Single (Investigator)
  measure: Change in MDS-Unified (PD)
  time frame: 1st, 45 and 90 days
  description: scale (MDS- UPDRS) the sum of parts I, II and III ranges from 0 to 176. The MDS-UPDRS score has three components, each consisting of questions with 0-4 point scale. Part I assesses mentation, behavior, and mood; Part II assesses activities of daily; and Part III assesses motor abilities. Where 0 represents the absence of impairment and 4 represents the highest degree of impairment.
  measure: Change in quality of life scale (PD)
  time frame: 1st, 45 and 90 days
  description: Questionnaire (PDQ-39) that will evaluate their health and overall quality of life. The total of 39 aspects of quality of life, maximum score is 132. Each aspect is rated on scale of 0 (best outcome) to 4 (worst outcome). A higher score or increased score compared to a previous visit indicates a lowered quality of life.
  measure: Changes in anxiety levels (PD&AD)
  time frame: 1st, 45 and 90 days
  description: Changes in anxiety levels, mood improvement and caregiver burden will be determined by applying the Neuropsychiatric Questionnaire (NPI-Q)
  measure: Changes in cognitive status measured by brief battery (AD)
  time frame: 1st, 45 and 90 days
  description: Mini Mental State Examination (MMSE): maximum score 30 points. Higher values indicate greater cognitive performance.
  measure: Change in Quality of Life (QOL) (AD)
  time frame: 1st, 45 and 90 days
  description: 13-item QOL-AD scale (total score range 13-52; higher scores indicate better QOL). The QOL-AD scale uses 1-4 (poor, fair, good, or excellent) to rate a variety of life domains, including the patient's physical health, mood, relationships, activities, and ability to complete tasks.
  measure: Change in cortisol dosage (Parkinson's and Alzheimer's group)
  time frame: 1st, 45 and 90 days
  description: Determination of cortisol levels can be used as an indirect measurement of emotional stress. Reduced levels of this hormone are related to reduced cardiovascular risk and reduced inflammatory damage.
  arm group label: Arm 1 - volunteers with parkinson's disease
  arm group type: Active Comparator
  description: 26 patients in this arm. in this arm will receive the probiotic K10 (2mg/kg/dia).
  arm group label: Arm 2 - volunteers with parkinson's disease
  arm group type: Placebo Comparator
  description: 26 patients in this arm. In this arm will receive the controlled placebo.
  arm group label: Arm 3- volunteers with alzheimer's disease
  arm group type: Active Comparator
  description: 26 patients in this arm. in this arm will receive the probiotic K10 (2mg/kg/dia).
  arm group label: Arm 4- volunteers with alzheimer's disease
  arm group type: Placebo Comparator
  description: 26 patients in this arm. In this arm will receive the controlled placebo.
  intervention type: Dietary Supplement
  intervention name: Probiotic K10
  description: clinical trial using 90 days of probiotic K10
  arm group label: Arm 1 - volunteers with parkinson's disease
  arm group label: Arm 3- volunteers with alzheimer's disease
  other name: Cerenovex
  other name: Neurobiotic
  intervention type: Drug
  intervention name: Placebo
  description: clinical trial using 90 days of placebo controlled
  arm group label: Arm 2 - volunteers with parkinson's disease
  arm group label: Arm 4- volunteers with alzheimer's disease
  other name: flour
  criteria: 
  gender: All
  gender based: Yes
  gender description: Parkinson under 18 years. Alzheimer between 60 and 85 years
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: No
  last name: Alyne M Ton, post-doc
  role: Principal Investigator
  affiliation: Gon1 Gestora de Projetos
  last name: Roberto S Badaró, post-doc
  role: Study Director
  affiliation: SENAI CIMATEC
  facility: 
  country: Brazil
  citation: Mazloom Z, Yousefinejad A, Dabbaghmanesh MH. Effect of probiotics on lipid profile, glycemic control, insulin action, oxidative stress, and inflammatory markers in patients with type 2 diabetes: a clinical trial. Iran J Med Sci. 2013 Mar;38(1):38-43.
  PMID: 23645956
  citation: Liu Z, Li T, Li P, Wei N, Zhao Z, Liang H, Ji X, Chen W, Xue M, Wei J. The Ambiguous Relationship of Oxidative Stress, Tau Hyperphosphorylation, and Autophagy Dysfunction in Alzheimer's Disease. Oxid Med Cell Longev. 2015;2015:352723. doi: 10.1155/2015/352723. Epub 2015 Jun 15.
  PMID: 26171115
  citation: Mishra V, Shah C, Mokashe N, Chavan R, Yadav H, Prajapati J. Probiotics as potential antioxidants: a systematic review. J Agric Food Chem. 2015 Apr 15;63(14):3615-26. doi: 10.1021/jf506326t. Epub 2015 Apr 6.
  PMID: 25808285
  citation: Licker V, Kovari E, Hochstrasser DF, Burkhard PR. Proteomics in human Parkinson's disease research. J Proteomics. 2009 Nov 2;73(1):10-29. doi: 10.1016/j.jprot.2009.07.007. Epub 2009 Jul 24.
  PMID: 19632367
  citation: Alexander GE, Crutcher MD, DeLong MR. Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. Prog Brain Res. 1990;85:119-46.
  PMID: 2094891
  citation: Obeso JA, Rodriguez-Oroz MC, Chana P, Lera G, Rodriguez M, Olanow CW. The evolution and origin of motor complications in Parkinson's disease. Neurology. 2000;55(11 Suppl 4):S13-20; discussion S21-3.
  PMID: 11147505
  citation: Sood B, Keenaghan M. Coenzyme Q10. 2022 Jan 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK531491/
  PMID: 30285386
  citation: Arenas-Jal M, Sune-Negre JM, Garcia-Montoya E. Coenzyme Q10 supplementation: Efficacy, safety, and formulation challenges. Compr Rev Food Sci Food Saf. 2020 Mar;19(2):574-594. doi: 10.1111/1541-4337.12539. Epub 2020 Feb 19.
  PMID: 33325173
  citation: Garrido-Maraver J, Cordero MD, Oropesa-Avila M, Vega AF, de la Mata M, Pavon AD, Alcocer-Gomez E, Calero CP, Paz MV, Alanis M, de Lavera I, Cotan D, Sanchez-Alcazar JA. Clinical applications of coenzyme Q10. Front Biosci (Landmark Ed). 2014 Jan 1;19(4):619-33. doi: 10.2741/4231.
  PMID: 24389208
  citation: Valentini L, Pinto A, Bourdel-Marchasson I, Ostan R, Brigidi P, Turroni S, Hrelia S, Hrelia P, Bereswill S, Fischer A, Leoncini E, Malaguti M, Blanc-Bisson C, Durrieu J, Spazzafumo L, Buccolini F, Pryen F, Donini LM, Franceschi C, Lochs H. Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The "RISTOMED project": Randomized controlled trial in healthy older people. Clin Nutr. 2015 Aug;34(4):593-602. doi: 10.1016/j.clnu.2014.09.023. Epub 2014 Oct 8.
  PMID: 25453395
  citation: Padurariu M, Ciobica A, Lefter R, Serban IL, Stefanescu C, Chirita R. The oxidative stress hypothesis in Alzheimer's disease. Psychiatr Danub. 2013 Dec;25(4):401-9.
  PMID: 24247053
  citation: Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog Neurobiol. 2001 Oct;65(2):135-72. doi: 10.1016/s0301-0082(01)00003-x.
  PMID: 11403877
  responsible party type: Sponsor-Investigator
  investigator affiliation: Gon1 Gestao de Projetos
  investigator full name: Deivis de Oliveira guimaraes
  investigator title: CRO general manager
  mesh term: Parkinson Disease
  mesh term: Alzheimer Disease
  sharing ipd: Yes
  ipd description: We can share all data regarding data collection, preserving the personal data of volunteers and as long as the request does not go beyond the limits of confidentiality, integrity and ethics.
  ipd info type: Study Protocol
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: They will be available after data collection and analysis, and will be abble for 1 year after the trial end.
  ipd access criteria: will be available upon request and for exclusive access to scientists, governmental and scientific organizations.
  ipd url: http://www.gon1.com.br/ipd
  provided document: 