<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/NCT01724476</url>
  </required_header>
  <id_info>
    <org_study_id>2011P002667</org_study_id>
    <secondary_id>2011D003142</secondary_id>
    <nct_id>NCT01724476</nct_id>
  </id_info>
  <brief_title>A Trial of Folate With B12 in Patients With Schizophrenia With Residual Symptoms in Ethiopia</brief_title>
  <official_title>A Placebo-Controlled Trial of Folate With B12 in Patients With Schizophrenia With Residual Symptoms in Ethiopia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Addis Ababa University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Amanuel Mental Hospital, Addis Ababa, Ethiopia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators propose to conduct a randomized Sequential Parallel Design for Double-Blind&#xD;
      Phase fixed dose, 4-month trial of folate plus B12 as add-on therapy in 200 Ethiopian&#xD;
      subjects with schizophrenia with stable residual positive or negative symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a 16-week, randomized, double-blind, placebo-controlled study of Folate 2mg plus B12&#xD;
      400mcg, as an adjunctive therapy in approximately 240 consecutive outpatients with&#xD;
      schizophrenia from Amanuel Hospital, which is based at Addis Ababa, Ethiopia will be enrolled&#xD;
      and screened for eligibility. The goal is to randomize and complete 200 subjects from the 240&#xD;
      enrolled. A Sequential Parallel Design for Double-Blind Phase will be utilized. During the&#xD;
      first phase of double-blind adjunctive treatment, eligible patients (n=200) are randomized to&#xD;
      adjunctive treatment with either folate and vitamin B12 (n=60) or placebo (n=150), with a&#xD;
      2:3:3 ratio for random assignment to the treatment sequences drug/drug (DD; n=70),&#xD;
      placebo/placebo (PP; n=70), and placebo/drug (PD; n=75), while all continue to receive their&#xD;
      antipsychotic agent for the entire duration of the study. Assuming a 10% drop-out rate during&#xD;
      the first phase, 126 patients on placebo will complete the first 56-day phase, and 54&#xD;
      patients on folate and vitamin B12 will complete the first 56-day phase.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2014</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in symptoms of schizophrenia as measured by the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>Examine the efficacy of a four-month trial of folate supplementation with B12 for potentially reducing symptoms of schizophrenia as measured by the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in psychotic symptoms as measured by the PANSS psychosis subscale score</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>Examine the efficacy of folate supplementation with B12 for psychotic symptoms as measured by the PANSS psychosis subscale score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in negative symptoms as measured by the Scale for Assessment of Negative Symptoms (SANS)</measure>
    <time_frame>Baseline to Week 16</time_frame>
    <description>Examine the efficacy of folate supplementation with B12 for negative symptoms as measured by the modified Scale for Assessment of Negative Symptoms (SANS) total score</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">200</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>folate with B12</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to the folate with B12 group will take 1 capsule of 400mcg per day of folate with B12.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to the placebo group will take 1 capsule of placebo per day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>folate with B12</intervention_name>
    <arm_group_label>folate with B12</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of schizophrenia, any subtype&#xD;
&#xD;
          2. Male or female&#xD;
&#xD;
          3. Age 18-65 years&#xD;
&#xD;
          4. Treated with an antipsychotic for at least 6 months at a stable dose for at least 6&#xD;
             weeks&#xD;
&#xD;
          5. PANSS total score of at least 60, with at least a 3 (moderate) on one negative symptom&#xD;
             item or on one positive symptom item.&#xD;
&#xD;
          6. No acute medical problems; any chronic medical condition (e.g. hypertension)&#xD;
             consistently treated and stable during the 1 month prior to participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable to provide informed consent&#xD;
&#xD;
          2. Serum B12 concentration less than 300mcg/L; Complete Blood Count (CBC) results&#xD;
             consistent with megaloblastic anemia&#xD;
&#xD;
          3. Serum creatinine concentration greater than 1.4&#xD;
&#xD;
          4. Current use of folate or B12 supplementation&#xD;
&#xD;
          5. Current use of any of the following medications: phenobarbital, phenytoin,&#xD;
             carbamazepine, valproic acid, fosphenytoin, primidone or pyrimethamine; antimalarial&#xD;
             drugs&#xD;
&#xD;
          6. Alcohol or other substance abuse within 3 months (nicotine allowed)&#xD;
&#xD;
          7. Subjects with a history of clinically significant neurological, metabolic, hepatic,&#xD;
             renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological&#xD;
             disorders (e.g. unstable angina, decompensated congestive heart failure, Central&#xD;
             Nervous System (CNS) infection or history of HIV seropositivity), which would pose a&#xD;
             risk to the patient if they were to participate in the study or that might confound&#xD;
             the results of the study. Active medical conditions that are minor or well controlled&#xD;
             are not exclusionary if they do not affect risk to the patient or the study results.&#xD;
             For example, the following are not exclusionary: a) stable and well- controlled&#xD;
             hypertension; b) asthma (no serious attacks in the past year)&#xD;
&#xD;
          8. Unstable psychiatric illness&#xD;
&#xD;
          9. Seizure disorder&#xD;
&#xD;
         10. Pregnancy or nursing&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gregory Fricchione, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Amanuel Mental Hospital</name>
      <address>
        <city>Addis Ababa</city>
        <country>Ethiopia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ethiopia</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>November 7, 2012</study_first_submitted>
  <study_first_submitted_qc>November 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 9, 2012</study_first_posted>
  <last_update_submitted>August 14, 2018</last_update_submitted>
  <last_update_submitted_qc>August 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Gregory Fricchione</investigator_full_name>
    <investigator_title>Director, Chester M. Pierce, MD Division of Global Psychiatry</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_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/NCT01724476
org study id: 2011P002667
secondary id: 2011D003142
nct id: NCT01724476
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
The investigators propose to conduct a randomized Sequential Parallel Design for Double-Blind
      Phase fixed dose, 4-month trial of folate plus B12 as add-on therapy in 200 Ethiopian
      subjects with schizophrenia with stable residual positive or negative symptoms.
This is a 16-week, randomized, double-blind, placebo-controlled study of Folate 2mg plus B12
      400mcg, as an adjunctive therapy in approximately 240 consecutive outpatients with
      schizophrenia from Amanuel Hospital, which is based at Addis Ababa, Ethiopia will be enrolled
      and screened for eligibility. The goal is to randomize and complete 200 subjects from the 240
      enrolled. A Sequential Parallel Design for Double-Blind Phase will be utilized. During the
      first phase of double-blind adjunctive treatment, eligible patients (n=200) are randomized to
      adjunctive treatment with either folate and vitamin B12 (n=60) or placebo (n=150), with a
      2:3:3 ratio for random assignment to the treatment sequences drug/drug (DD; n=70),
      placebo/placebo (PP; n=70), and placebo/drug (PD; n=75), while all continue to receive their
      antipsychotic agent for the entire duration of the study. Assuming a 10% drop-out rate during
      the first phase, 126 patients on placebo will complete the first 56-day phase, and 54
      patients on folate and vitamin B12 will complete the first 56-day phase.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in symptoms of schizophrenia as measured by the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score
time frame: Baseline to Week 16
description: Examine the efficacy of a four-month trial of folate supplementation with B12 for potentially reducing symptoms of schizophrenia as measured by the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score
measure: Change in psychotic symptoms as measured by the PANSS psychosis subscale score
time frame: Baseline to Week 16
description: Examine the efficacy of folate supplementation with B12 for psychotic symptoms as measured by the PANSS psychosis subscale score
measure: Change in negative symptoms as measured by the Scale for Assessment of Negative Symptoms (SANS)
time frame: Baseline to Week 16
description: Examine the efficacy of folate supplementation with B12 for negative symptoms as measured by the modified Scale for Assessment of Negative Symptoms (SANS) total score
arm group label: folate with B12
arm group type: Active Comparator
description: Subjects randomized to the folate with B12 group will take 1 capsule of 400mcg per day of folate with B12.
arm group label: placebo
arm group type: Placebo Comparator
description: Subjects randomized to the placebo group will take 1 capsule of placebo per day.
intervention type: Drug
intervention name: folate with B12
arm group label: folate with B12
intervention type: Drug
intervention name: placebo
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Gregory Fricchione, MD
role: Principal Investigator
affiliation: Massachusetts General Hospital
facility: 
country: Ethiopia
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Gregory Fricchione
investigator title: Director, Chester M. Pierce, MD Division of Global Psychiatry
mesh term: Schizophrenia