<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/NCT04453306</url>
  </required_header>
  <id_info>
    <org_study_id>140228</org_study_id>
    <nct_id>NCT04453306</nct_id>
  </id_info>
  <brief_title>Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome</brief_title>
  <official_title>Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome: a Double-blind Placebo-controlled Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Treatment of obesity related to Polycystic Ovary Syndrome with topiramate or placebo to&#xD;
      assess improvement of clinical and laboratory parameters after 6 months of follow-up&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomized double blind placebo-controlled clinical trial. Polycystic ovary syndrome (PCOS)&#xD;
      is a frequent endocrinopathy, affecting more than 10% of women of reproductive age. It is&#xD;
      associated with a higher prevalence of obesity and insulin resistance, with a higher risk for&#xD;
      diabetes, dyslipidemia and hypertension. Topiramate is a drug used in the treatment of&#xD;
      epilepsy and migraine prophylaxis since the 1990s and several studies show an association&#xD;
      with weight loss. This medicine is administered in combination with phentermine in other&#xD;
      countries, with variable weight loss. Despite evidence of the benefit of topiramate for&#xD;
      weight loss, there is still no record of studies evaluating this drug in patients with PCOS&#xD;
      for the treatment of obesity. The objective of this project is to evaluate the results of&#xD;
      treatment with topiramate in terms of weight reduction, reduction of serum androgens and&#xD;
      changes in body composition, in patients with PCOS and obese, associated with a low-calorie&#xD;
      diet, over a period of six months. Eighty patients with PCOS (18 to 40 years old) seen at the&#xD;
      HCPA Endocrinology Service outpatient clinic who are overweight with a BMI&gt; or = 27 kg / m2&#xD;
      associated with at least one comorbidity or obesity (BMI 30-40) will be included. Patients&#xD;
      will be randomized to 2 groups: Topiramate and Placebo and the 2 groups will receive a&#xD;
      low-calorie diet.&#xD;
&#xD;
      Anthropometric, clinical, hormonal, nutritional and body composition assessment will be&#xD;
      performed before, during and after treatments. It is expected to determine whether the&#xD;
      addition of topiramate to dietary treatment can improve metabolic, hormonal and weight loss&#xD;
      outcomes in women with PCOS.&#xD;
&#xD;
      Research Objective: General objective: To evaluate the results of treatment with topiramate&#xD;
      in patients with PCOS and obese, associated with a low-calorie diet, in six months of&#xD;
      treatment.&#xD;
&#xD;
      Specific objectives: To evaluate the response to the proposed treatment in terms of weight&#xD;
      reduction and body mass index (BMI), reduction of serum androgens, changes in body&#xD;
      composition, in addition to assessing minor psychiatric disorders possibly associated through&#xD;
      the Self-Reporting screening questionnaire. Questionnaire (SRQ-20).&#xD;
&#xD;
      Assessment of Risks and Benefits: The risks of the project are mainly related to the use of&#xD;
      the drug topiramate. This drug has an extensive list of adverse effects, in addition to the&#xD;
      side effect on appetite and weight, the most common are paresthesias, drowsiness, lethargy,&#xD;
      attention disorder, mood disorders, depression, taste changes and psychomotor disorders.&#xD;
      However, studies show that the majority of adverse reactions were mild to moderate in&#xD;
      severity. Other risks inherent to the study are the absence of previous studies in the target&#xD;
      population and discomfort in relation to the number of visits, additional tests and blood&#xD;
      samples for an extended period of 6 months. The benefits of the study are related to the&#xD;
      acquisition of knowledge and the likely positive results may benefit future patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 2014</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</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>
    <intervention_model_description>Double-blind Placebo-controlled Clinical Trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>participants, caregivers, researchers and outcome assessors are blinded to the medications participants are receiving. Participants receive pills with identical size, color and taste between the placebo and the active drug.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change of Body Mass index (BMi) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>change of Body Mass index (BMi) in kg/m² from the baseline; weight and height will be combined to report BMI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in the modified Ferriman-Gallwey Hirsutism Score (mFG) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>In the modified method, hair growth is rated from 0 (no growth of terminal hair) to 4 (extensive hair growth) in each of the nine locations (Upper lip, Chin, Chest, Upper back, Lower back, Upper abdomen, Lower abdomen, Upper arms, Thighs). A patient's score may therefore range from a minimum score of 0 to a maximum score of 36. A score of 6 or higher will be adopted as indicative of androgen excess.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of testosterone at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change of testosterone (ng/mL) at 6 months from the baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of glucose at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change of glucose(mg/dL) at 6 months from the baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of triglyceride at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change of triglyceride (mg/dL) at 6 months from the baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of High-density lipoprotein (HDL) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change of HDL cholesterol (mg/dL) at 6 months from the baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of total cholesterol at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change of total cholesterol (mg/dL) at 6 months from the baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of Low-density lipoprotein (LDL) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change of LDL cholesterol (mg/dL) at 6 months from the baseline. LDL cholesterol will be calculated with the Friedewald formula, an estimation of LDL-c level that uses the following levels of total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-c): LDL-c (mg/dL) = TC (mg/dL) - HDL-c (mg/dL) - TG (mg/dL)/5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of homeostatic model assessment (HOMA-IR) at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change of HOMA-IR at 6 months from the baseline. HOMA-IR will be calculated according to the formula: fasting insulin (µU/L) x fasting glucose (nmol/L)/22.5.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in systolic blood pressure at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>change in systolic blood pressure (mmHg) at 6 months from baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>change in diastolic blood pressure at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>change in diastolic blood pressure (mmHg) at 6 months from baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>change of body composition at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change in body composition evaluated through Dual-energy X-ray absorptiometry (DXA) from the baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in anxiety score at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Change in anxiety score, assessed through the self-report questionnaire-20 (SRQ 20), consisting of 20 questions with a yes / no answer, assigning 1 point to the &quot;yes&quot; answer. A cut-off point of 8 or more indicates an anxiety disorder, with a minimum of zero and a maximum of 20 points.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Obesity</condition>
  <condition>Polycystic Ovary Syndrome</condition>
  <condition>Hyperandrogenism</condition>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients with the same characteristics as the intervention group. Bottles containing 30 white and green tablets are provided to the participants. The number of bottles is anticipated according to the day of the next appointment. Patients should take 2 tablets bedtime with a full glass of water.&#xD;
Bottles are labeled as TPMT100 or TPMT200. The dosage of each tablet is 25 mg, totaling 50 mg / day. The dosage is doubled at 3 months if the patient does not lose at least 3% of the initial weight.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with the same characteristics as the placebo group. Bottles containing 30 white and green tablets are provided to the participants. The number of bottles is anticipated according to the day of the next appointment. Patients should take 2 tablets bedtime with a full glass of water.&#xD;
Bottles are labeled as TPMT100 or TPMT200. The dosage of each tablet is 25 mg, totaling 50 mg / day. The dosage is doubled at 3 months if the patient does not lose at least 3% of the initial weight.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topiramate</intervention_name>
    <description>topiramate 25mg is coated in tablets in an independent laboratory</description>
    <arm_group_label>intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>innocuous substance is coated in tablets in an independent laboratory</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age between 18 and 40 years&#xD;
&#xD;
          -  diagnostic criteria for PCOS&#xD;
&#xD;
          -  overweight with a BMI ≥ 27 kg / m² associated with at least one comorbidity&#xD;
             (hypertension, type 2 diabetes mellitus, dyslipidemia) or obesity with a BMI between&#xD;
             30 and 45 kg / m² with or without comorbidities&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  severe systemic arterial hypertension (≥180 / 100 mmHg)&#xD;
&#xD;
          -  pregnant or lactating women&#xD;
&#xD;
          -  diabetics using sulfonylurea or insulin&#xD;
&#xD;
          -  any known allergy or intolerance to topiramate medication&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Poli Mara Spritzer</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of Rio Grande do Sul</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lucas Marchesan</last_name>
    <phone>+55 51 993873838</phone>
    <email>lucas.iuk@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hospital de Clínicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90035-007</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lucas B Marchesan</last_name>
      <phone>+55 51 993873838</phone>
      <email>lucas.iuk@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>June 26, 2020</last_update_submitted>
  <last_update_submitted_qc>June 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polycystic Ovary Syndrome</mesh_term>
    <mesh_term>Hyperandrogenism</mesh_term>
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Topiramate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04453306
org study id: 140228
nct id: NCT04453306
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Treatment of obesity related to Polycystic Ovary Syndrome with topiramate or placebo to
      assess improvement of clinical and laboratory parameters after 6 months of follow-up
Randomized double blind placebo-controlled clinical trial. Polycystic ovary syndrome (PCOS)
      is a frequent endocrinopathy, affecting more than 10% of women of reproductive age. It is
      associated with a higher prevalence of obesity and insulin resistance, with a higher risk for
      diabetes, dyslipidemia and hypertension. Topiramate is a drug used in the treatment of
      epilepsy and migraine prophylaxis since the 1990s and several studies show an association
      with weight loss. This medicine is administered in combination with phentermine in other
      countries, with variable weight loss. Despite evidence of the benefit of topiramate for
      weight loss, there is still no record of studies evaluating this drug in patients with PCOS
      for the treatment of obesity. The objective of this project is to evaluate the results of
      treatment with topiramate in terms of weight reduction, reduction of serum androgens and
      changes in body composition, in patients with PCOS and obese, associated with a low-calorie
      diet, over a period of six months. Eighty patients with PCOS (18 to 40 years old) seen at the
      HCPA Endocrinology Service outpatient clinic who are overweight with a BMI> or = 27 kg / m2
      associated with at least one comorbidity or obesity (BMI 30-40) will be included. Patients
      will be randomized to 2 groups: Topiramate and Placebo and the 2 groups will receive a
      low-calorie diet.

      Anthropometric, clinical, hormonal, nutritional and body composition assessment will be
      performed before, during and after treatments. It is expected to determine whether the
      addition of topiramate to dietary treatment can improve metabolic, hormonal and weight loss
      outcomes in women with PCOS.

      Research Objective: General objective: To evaluate the results of treatment with topiramate
      in patients with PCOS and obese, associated with a low-calorie diet, in six months of
      treatment.

      Specific objectives: To evaluate the response to the proposed treatment in terms of weight
      reduction and body mass index (BMI), reduction of serum androgens, changes in body
      composition, in addition to assessing minor psychiatric disorders possibly associated through
      the Self-Reporting screening questionnaire. Questionnaire (SRQ-20).

      Assessment of Risks and Benefits: The risks of the project are mainly related to the use of
      the drug topiramate. This drug has an extensive list of adverse effects, in addition to the
      side effect on appetite and weight, the most common are paresthesias, drowsiness, lethargy,
      attention disorder, mood disorders, depression, taste changes and psychomotor disorders.
      However, studies show that the majority of adverse reactions were mild to moderate in
      severity. Other risks inherent to the study are the absence of previous studies in the target
      population and discomfort in relation to the number of visits, additional tests and blood
      samples for an extended period of 6 months. The benefits of the study are related to the
      acquisition of knowledge and the likely positive results may benefit future patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double-blind Placebo-controlled Clinical Trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: participants, caregivers, researchers and outcome assessors are blinded to the medications participants are receiving. Participants receive pills with identical size, color and taste between the placebo and the active drug.
measure: Change of Body Mass index (BMi) at 6 months
time frame: 6 months
description: change of Body Mass index (BMi) in kg/m² from the baseline; weight and height will be combined to report BMI
measure: change in the modified Ferriman-Gallwey Hirsutism Score (mFG) at 6 months
time frame: 6 months
description: In the modified method, hair growth is rated from 0 (no growth of terminal hair) to 4 (extensive hair growth) in each of the nine locations (Upper lip, Chin, Chest, Upper back, Lower back, Upper abdomen, Lower abdomen, Upper arms, Thighs). A patient's score may therefore range from a minimum score of 0 to a maximum score of 36. A score of 6 or higher will be adopted as indicative of androgen excess.
measure: Change of testosterone at 6 months
time frame: 6 months
description: Change of testosterone (ng/mL) at 6 months from the baseline
measure: Change of glucose at 6 months
time frame: 6 months
description: Change of glucose(mg/dL) at 6 months from the baseline
measure: Change of triglyceride at 6 months
time frame: 6 months
description: Change of triglyceride (mg/dL) at 6 months from the baseline
measure: Change of High-density lipoprotein (HDL) at 6 months
time frame: 6 months
description: Change of HDL cholesterol (mg/dL) at 6 months from the baseline
measure: Change of total cholesterol at 6 months
time frame: 6 months
description: Change of total cholesterol (mg/dL) at 6 months from the baseline
measure: Change of Low-density lipoprotein (LDL) at 6 months
time frame: 6 months
description: Change of LDL cholesterol (mg/dL) at 6 months from the baseline. LDL cholesterol will be calculated with the Friedewald formula, an estimation of LDL-c level that uses the following levels of total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-c): LDL-c (mg/dL) = TC (mg/dL) - HDL-c (mg/dL) - TG (mg/dL)/5
measure: Change of homeostatic model assessment (HOMA-IR) at 6 months
time frame: 6 months
description: Change of HOMA-IR at 6 months from the baseline. HOMA-IR will be calculated according to the formula: fasting insulin (µU/L) x fasting glucose (nmol/L)/22.5.
measure: change in systolic blood pressure at 6 months
time frame: 6 months
description: change in systolic blood pressure (mmHg) at 6 months from baseline.
measure: change in diastolic blood pressure at 6 months
time frame: 6 months
description: change in diastolic blood pressure (mmHg) at 6 months from baseline.
measure: change of body composition at 6 months
time frame: 6 months
description: Change in body composition evaluated through Dual-energy X-ray absorptiometry (DXA) from the baseline
measure: Change in anxiety score at 6 months
time frame: 6 months
description: Change in anxiety score, assessed through the self-report questionnaire-20 (SRQ 20), consisting of 20 questions with a yes / no answer, assigning 1 point to the "yes" answer. A cut-off point of 8 or more indicates an anxiety disorder, with a minimum of zero and a maximum of 20 points.
arm group label: placebo
arm group type: Placebo Comparator
description: Patients with the same characteristics as the intervention group. Bottles containing 30 white and green tablets are provided to the participants. The number of bottles is anticipated according to the day of the next appointment. Patients should take 2 tablets bedtime with a full glass of water.
Bottles are labeled as TPMT100 or TPMT200. The dosage of each tablet is 25 mg, totaling 50 mg / day. The dosage is doubled at 3 months if the patient does not lose at least 3% of the initial weight.
arm group label: intervention
arm group type: Experimental
description: Patients with the same characteristics as the placebo group. Bottles containing 30 white and green tablets are provided to the participants. The number of bottles is anticipated according to the day of the next appointment. Patients should take 2 tablets bedtime with a full glass of water.
Bottles are labeled as TPMT100 or TPMT200. The dosage of each tablet is 25 mg, totaling 50 mg / day. The dosage is doubled at 3 months if the patient does not lose at least 3% of the initial weight.
intervention type: Drug
intervention name: Topiramate
description: topiramate 25mg is coated in tablets in an independent laboratory
arm group label: intervention
intervention type: Drug
intervention name: Placebo
description: innocuous substance is coated in tablets in an independent laboratory
arm group label: placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: No
last name: Poli Mara Spritzer
role: Principal Investigator
affiliation: Federal University of Rio Grande do Sul
last name: Lucas Marchesan
phone: +55 51 993873838
email: lucas.iuk@gmail.com
facility: 
status: Recruiting
contact: 
country: Brazil
responsible party type: Sponsor
mesh term: Polycystic Ovary Syndrome
mesh term: Hyperandrogenism
mesh term: Obesity
mesh term: Syndrome
mesh term: Topiramate
sharing ipd: Undecided