<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/NCT01672372</url>
  </required_header>
  <id_info>
    <org_study_id>20091119</org_study_id>
    <nct_id>NCT01672372</nct_id>
  </id_info>
  <brief_title>The Effect of Methylated Vitamin B Complex on Depression</brief_title>
  <official_title>The Effect of Methylated Vitamin B Complex on Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Premier Research Labs</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The proposed study is a 60-day, randomized, double-blind, placebo-controlled trial to&#xD;
      evaluate the efficacy of a methylated vitamin B complex nutritional supplement (Max Stress&#xD;
      B™) for improving depressive and anxiety symptoms according to the Beck Depression and&#xD;
      Anxiety Inventories, respectively, in 60 patients (18+ years of age) diagnosed with major&#xD;
      depression or other forms of depressive disorders and an elevated level of homocysteine (&gt; 10&#xD;
      µmol/L) at baseline. Secondary outcomes will include anthropometrics for body composition,&#xD;
      blood pressure and pulse, level of physical activity, dietary intake, and quality of life.&#xD;
      Participants will be assessed at baseline and 30 and 60 days. The study will consist of two&#xD;
      treatment arms: (a) vitamin B complex nutritional supplement and (b) placebo.&#xD;
&#xD;
      The information obtained in this study will help in determining the efficacy of using&#xD;
      nutritional supplements for improving the outcomes of people with depression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design Potential participants will be identified through referrals from the offices of&#xD;
      Dr. Woolger, the UM Department of Psychiatry Clinics, the Medical Wellness Center, and the&#xD;
      Center for Complementary and Integrative Medicine. Drs. Woolger and Konefal will conduct a&#xD;
      preliminary screening of their clients to determine if the potential participant meets the&#xD;
      inclusion criteria to participate in the study. Dr. Lewis, Messrs. Long, Dicenso, or Bregman,&#xD;
      or Mses. Hoffman, Rafatjah, Melillo, Ko, Alonso, or McCurdy will conduct preliminary&#xD;
      screenings through the Medical Wellness Center or the Center for Complementary and&#xD;
      Integrative Medicine. Once accepted into the study, participants will then contact Dr. Lewis,&#xD;
      Messrs. Long, Dicenso, or Bregman, or Mses. Hoffman, Rafatjah, Melillo, Ko, Alonso, or&#xD;
      McCurdy for informed consent and study protocol procedures. Subjects will then be assigned to&#xD;
      one of the two study conditions. Assignment of subjects to treatment groups will be done by&#xD;
      following a table of random permutations, which will balance the number of subjects in each&#xD;
      group. The table will be prepared in advance by a random number generating program.&#xD;
&#xD;
      Participants Sixty subjects (30 in each condition) with depression will participate in this&#xD;
      study. Subjects will be primarily those who have expressed an interest in trying&#xD;
      non-medication or integrative treatment approaches for their depression.&#xD;
&#xD;
      Initial visit The study will be fully explained to each potential participant, and a written&#xD;
      informed consent will be obtained before beginning the intervention. Dr. Lewis, Messrs. Long,&#xD;
      Dicenso, or Bregman, or Mses. Hoffman, Rafatjah, Melillo, Ko, Alonso, or McCurdy will&#xD;
      administer all of the assessments at baseline and follow-up and will notify the subjects of&#xD;
      the time to return for the follow-up appointments.&#xD;
&#xD;
      Intervention Participants enrolled in the study will receive either the Max Stress B™ at a&#xD;
      dosage level of ½ teaspoon twice daily or the placebo for the 60-day treatment period.&#xD;
      Subjects will not be advised to modify eating or physical activity habits or non-depression&#xD;
      prescription medication use. Subjects will not be allowed to use depression-treatment&#xD;
      medication starting at 2 weeks before beginning the intervention and until the conclusion of&#xD;
      the 60-day treatment period. Subjects will be instructed not to consume any other nutritional&#xD;
      supplements containing any of the vitamin B complex nutrients, SAMe, inositol, PABA, or&#xD;
      folate for two weeks prior to having the baseline assessments and until the conclusion of the&#xD;
      60-day period. Because of how Max Stress B™ is produced by Premier Research Labs, consuming&#xD;
      the Max Stress B™ should be well-tolerated. We are aware of no side effects of this&#xD;
      particular product. According to the company's literature, Max Stress B™ is a whole-nutrient&#xD;
      natural source extract from probiotic colonies that contains: vitamins B1, B2, B3, B5, B6,&#xD;
      and B12, and folate, PABA, biotin, inositol, purified water, and certified organic alcohol.&#xD;
      This product is documented online at the following web address: http://www.prlabs.com/ under&#xD;
      the &quot;Products&quot; tab, item #2352.&#xD;
&#xD;
      Outcomes and Assessments Each participant will complete a basic demographics and medical&#xD;
      history questionnaire to assess the importance of these background variables. They will also&#xD;
      be asked to list their current medications and note any changes in type or amount during the&#xD;
      course of the study. Blood pressure, heart rate, body weight and height, skinfold&#xD;
      assessments, and hip and waist circumference will be assessed by Dr. Lewis, Messrs. Long,&#xD;
      Dicenso, Bregman, or Reihm, or Mses. Rafatjah, Melillo, Ko, Alonso, or McCurdy at baseline&#xD;
      and 30- and 60-days follow-up.&#xD;
&#xD;
      Criteria used to select the assessment instruments included: a) appropriateness for the&#xD;
      population; b) ease of administration and scoring; c) experience administering these&#xD;
      measures; and d) employment of measures involving a multi-method (i.e., self-report and&#xD;
      physical measures) approach to enhance the validity of the overall assessment.&#xD;
&#xD;
      The following measures will be assessed:&#xD;
&#xD;
        1. The primary outcome of this study is depression level, assessed by the Beck Depression&#xD;
           Inventory II, which will be assessed to reflect its relationship to changes in dietary&#xD;
           patterns and physical activity. Because item 9 of the Beck Depression Inventory inquires&#xD;
           about &quot;Suicidal thoughts or wishes,&quot; we will immediately notify the attending physician&#xD;
           in the Crisis facility of UM/JMH if a subject responds affirmatively to this question,&#xD;
           which may be indicative of suicidal ideation (SI). Any spontaneous comments or&#xD;
           circumstances indicative of SI should be explored with the participant (e.g., &quot;life not&#xD;
           worth living,&quot; &quot;be better off dead,&quot; selling or giving away possessions, or withdrawing&#xD;
           from relationships, etc.). If suicidal ideation is present, the assessor will maintain&#xD;
           persistent contact with the subject until the physician can meet with the subject. If&#xD;
           the suicide threat is judged to be immediate by the physician (i.e., the subject&#xD;
           indicates current intent, has a plan, and available means) then the assessor will&#xD;
           maintain contact with the subject and ensure that the subject is taken to a psychiatric&#xD;
           emergency setting. The Jackson Crisis Mental Health Unit (305-355-7777) is a potential&#xD;
           emergency facility and is located at 1695 N.W. 9th Avenue at the back of the Mental&#xD;
           Health building.&#xD;
&#xD;
        2. The Beck Anxiety Inventory to assess the change in the participant's level of anxiety.&#xD;
&#xD;
        3. Physiological and anthropometric: Blood pressure and heart rate, body weight and height&#xD;
           to calculate body mass index (BMI), skinfold caliper assessment to calculate percent&#xD;
           body fat, waist and hip circumference to calculate waist to hip ratio at baseline and 60&#xD;
           days.&#xD;
&#xD;
        4. Physical activity: Physical activity will be assessed at baseline and 30- and 60-days&#xD;
           follow-up by the Stanford 7-day Activity Recall. This instrument assesses the amount&#xD;
           (number of hours) of moderate, physically challenging, and very physically challenging&#xD;
           activities over the past 7 days. This instrument provides useful estimates of habitual&#xD;
           physical activity for research, significantly agrees with daily self-report of physical&#xD;
           activity, and has been validated for use in community settings.&#xD;
&#xD;
        5. Quality of life: The SF-36v2™ Health Survey provides psychometrically-based physical and&#xD;
           mental health summary measures and a preference-based health utility index. It is a&#xD;
           generic measure that does not target a specific age, disease, or treatment group and&#xD;
           will be assessed at baseline and 30- and 60-days follow-up.&#xD;
&#xD;
      Participant Compensation Subjects will be compensated $40 for attending each assessment at&#xD;
      baseline and 30- and 60-days follow-up. This amount is intended to compensate for their time&#xD;
      and effort in completing the outcome and assessment measures. Therefore, a subject could&#xD;
      receive up to $120 for participating in the study. We believe this amount to be fair and not&#xD;
      to constitute coercion, given the commitment required for completing the entire protocol.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2011</start_date>
  <completion_date type="Actual">October 2011</completion_date>
  <primary_completion_date type="Actual">October 2011</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Depression level</measure>
    <time_frame>2 months</time_frame>
    <description>Assessed by the Beck Depression Inventory II, the Beck Anxiety Inventory, SF-36v2™ Health Survey, physiological and anthropometric measures&#xD;
Because item 9 of the Beck Depression Inventory inquires about &quot;Suicidal thoughts or wishes,&quot; we will immediately notify the attending physician in the Crisis facility of UM/JMH if a subject responds affirmatively to this question, which may be indicative of suicidal ideation (SI).</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Placebo Max Stress B</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>oil/water emulsion with food coloring to simulate actual product</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Max Stress B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>whole-nutrient natural source extract from probiotic colonies that contains vitamins B1, B2, B5, B6, B12, and folate, PABA, biotin, inositol, purified water and certified organic alcohol.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Max Stress B</intervention_name>
    <description>Participants are to mix one vial per day of either placebo or actual supplement in 1 liter of water and drink over the course of the day</description>
    <arm_group_label>Max Stress B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo Max Stress B</intervention_name>
    <arm_group_label>Placebo Max Stress B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women ages 18 years and over.&#xD;
&#xD;
          -  Individuals with a diagnosed type or form of depression.&#xD;
&#xD;
          -  An elevated level of homocysteine (&gt; 10 µmol/L) at screening.&#xD;
&#xD;
          -  Interest in participating in a novel nutritional supplement program.&#xD;
&#xD;
          -  Willingness to follow recommendations, including going off of all medication for&#xD;
             depression 2 weeks before starting vitamin B complex regimen.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Excluded in any of the above criteria are not met.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John E Lewis, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Miami CRB</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 21, 2012</study_first_submitted>
  <study_first_submitted_qc>August 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 24, 2012</study_first_posted>
  <last_update_submitted>August 4, 2014</last_update_submitted>
  <last_update_submitted_qc>August 4, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 6, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>John E. Lewis</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</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/NCT01672372
org study id: 20091119
nct id: NCT01672372
lead sponsor: 
collaborator: 
has dmc: Yes
The proposed study is a 60-day, randomized, double-blind, placebo-controlled trial to
      evaluate the efficacy of a methylated vitamin B complex nutritional supplement (Max Stress
      B™) for improving depressive and anxiety symptoms according to the Beck Depression and
      Anxiety Inventories, respectively, in 60 patients (18+ years of age) diagnosed with major
      depression or other forms of depressive disorders and an elevated level of homocysteine (> 10
      µmol/L) at baseline. Secondary outcomes will include anthropometrics for body composition,
      blood pressure and pulse, level of physical activity, dietary intake, and quality of life.
      Participants will be assessed at baseline and 30 and 60 days. The study will consist of two
      treatment arms: (a) vitamin B complex nutritional supplement and (b) placebo.

      The information obtained in this study will help in determining the efficacy of using
      nutritional supplements for improving the outcomes of people with depression.
Study Design Potential participants will be identified through referrals from the offices of
      Dr. Woolger, the UM Department of Psychiatry Clinics, the Medical Wellness Center, and the
      Center for Complementary and Integrative Medicine. Drs. Woolger and Konefal will conduct a
      preliminary screening of their clients to determine if the potential participant meets the
      inclusion criteria to participate in the study. Dr. Lewis, Messrs. Long, Dicenso, or Bregman,
      or Mses. Hoffman, Rafatjah, Melillo, Ko, Alonso, or McCurdy will conduct preliminary
      screenings through the Medical Wellness Center or the Center for Complementary and
      Integrative Medicine. Once accepted into the study, participants will then contact Dr. Lewis,
      Messrs. Long, Dicenso, or Bregman, or Mses. Hoffman, Rafatjah, Melillo, Ko, Alonso, or
      McCurdy for informed consent and study protocol procedures. Subjects will then be assigned to
      one of the two study conditions. Assignment of subjects to treatment groups will be done by
      following a table of random permutations, which will balance the number of subjects in each
      group. The table will be prepared in advance by a random number generating program.

      Participants Sixty subjects (30 in each condition) with depression will participate in this
      study. Subjects will be primarily those who have expressed an interest in trying
      non-medication or integrative treatment approaches for their depression.

      Initial visit The study will be fully explained to each potential participant, and a written
      informed consent will be obtained before beginning the intervention. Dr. Lewis, Messrs. Long,
      Dicenso, or Bregman, or Mses. Hoffman, Rafatjah, Melillo, Ko, Alonso, or McCurdy will
      administer all of the assessments at baseline and follow-up and will notify the subjects of
      the time to return for the follow-up appointments.

      Intervention Participants enrolled in the study will receive either the Max Stress B™ at a
      dosage level of ½ teaspoon twice daily or the placebo for the 60-day treatment period.
      Subjects will not be advised to modify eating or physical activity habits or non-depression
      prescription medication use. Subjects will not be allowed to use depression-treatment
      medication starting at 2 weeks before beginning the intervention and until the conclusion of
      the 60-day treatment period. Subjects will be instructed not to consume any other nutritional
      supplements containing any of the vitamin B complex nutrients, SAMe, inositol, PABA, or
      folate for two weeks prior to having the baseline assessments and until the conclusion of the
      60-day period. Because of how Max Stress B™ is produced by Premier Research Labs, consuming
      the Max Stress B™ should be well-tolerated. We are aware of no side effects of this
      particular product. According to the company's literature, Max Stress B™ is a whole-nutrient
      natural source extract from probiotic colonies that contains: vitamins B1, B2, B3, B5, B6,
      and B12, and folate, PABA, biotin, inositol, purified water, and certified organic alcohol.
      This product is documented online at the following web address: http://www.prlabs.com/ under
      the "Products" tab, item #2352.

      Outcomes and Assessments Each participant will complete a basic demographics and medical
      history questionnaire to assess the importance of these background variables. They will also
      be asked to list their current medications and note any changes in type or amount during the
      course of the study. Blood pressure, heart rate, body weight and height, skinfold
      assessments, and hip and waist circumference will be assessed by Dr. Lewis, Messrs. Long,
      Dicenso, Bregman, or Reihm, or Mses. Rafatjah, Melillo, Ko, Alonso, or McCurdy at baseline
      and 30- and 60-days follow-up.

      Criteria used to select the assessment instruments included: a) appropriateness for the
      population; b) ease of administration and scoring; c) experience administering these
      measures; and d) employment of measures involving a multi-method (i.e., self-report and
      physical measures) approach to enhance the validity of the overall assessment.

      The following measures will be assessed:

        1. The primary outcome of this study is depression level, assessed by the Beck Depression
           Inventory II, which will be assessed to reflect its relationship to changes in dietary
           patterns and physical activity. Because item 9 of the Beck Depression Inventory inquires
           about "Suicidal thoughts or wishes," we will immediately notify the attending physician
           in the Crisis facility of UM/JMH if a subject responds affirmatively to this question,
           which may be indicative of suicidal ideation (SI). Any spontaneous comments or
           circumstances indicative of SI should be explored with the participant (e.g., "life not
           worth living," "be better off dead," selling or giving away possessions, or withdrawing
           from relationships, etc.). If suicidal ideation is present, the assessor will maintain
           persistent contact with the subject until the physician can meet with the subject. If
           the suicide threat is judged to be immediate by the physician (i.e., the subject
           indicates current intent, has a plan, and available means) then the assessor will
           maintain contact with the subject and ensure that the subject is taken to a psychiatric
           emergency setting. The Jackson Crisis Mental Health Unit (305-355-7777) is a potential
           emergency facility and is located at 1695 N.W. 9th Avenue at the back of the Mental
           Health building.

        2. The Beck Anxiety Inventory to assess the change in the participant's level of anxiety.

        3. Physiological and anthropometric: Blood pressure and heart rate, body weight and height
           to calculate body mass index (BMI), skinfold caliper assessment to calculate percent
           body fat, waist and hip circumference to calculate waist to hip ratio at baseline and 60
           days.

        4. Physical activity: Physical activity will be assessed at baseline and 30- and 60-days
           follow-up by the Stanford 7-day Activity Recall. This instrument assesses the amount
           (number of hours) of moderate, physically challenging, and very physically challenging
           activities over the past 7 days. This instrument provides useful estimates of habitual
           physical activity for research, significantly agrees with daily self-report of physical
           activity, and has been validated for use in community settings.

        5. Quality of life: The SF-36v2™ Health Survey provides psychometrically-based physical and
           mental health summary measures and a preference-based health utility index. It is a
           generic measure that does not target a specific age, disease, or treatment group and
           will be assessed at baseline and 30- and 60-days follow-up.

      Participant Compensation Subjects will be compensated $40 for attending each assessment at
      baseline and 30- and 60-days follow-up. This amount is intended to compensate for their time
      and effort in completing the outcome and assessment measures. Therefore, a subject could
      receive up to $120 for participating in the study. We believe this amount to be fair and not
      to constitute coercion, given the commitment required for completing the entire protocol.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Depression level
time frame: 2 months
description: Assessed by the Beck Depression Inventory II, the Beck Anxiety Inventory, SF-36v2™ Health Survey, physiological and anthropometric measures
Because item 9 of the Beck Depression Inventory inquires about "Suicidal thoughts or wishes," we will immediately notify the attending physician in the Crisis facility of UM/JMH if a subject responds affirmatively to this question, which may be indicative of suicidal ideation (SI).
arm group label: Placebo Max Stress B
arm group type: Placebo Comparator
description: oil/water emulsion with food coloring to simulate actual product
arm group label: Max Stress B
arm group type: Experimental
description: whole-nutrient natural source extract from probiotic colonies that contains vitamins B1, B2, B5, B6, B12, and folate, PABA, biotin, inositol, purified water and certified organic alcohol.
intervention type: Dietary Supplement
intervention name: Max Stress B
description: Participants are to mix one vial per day of either placebo or actual supplement in 1 liter of water and drink over the course of the day
arm group label: Max Stress B
intervention type: Dietary Supplement
intervention name: Placebo Max Stress B
arm group label: Placebo Max Stress B
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John E Lewis, PhD
role: Principal Investigator
affiliation: University of Miami
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Miami
investigator full name: John E. Lewis
investigator title: Associate Professor
mesh term: Depression
mesh term: Depressive Disorder