Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome

Sponsor
Hospital de Clinicas de Porto Alegre (Other)
Overall Status
Unknown status
CT.gov ID
NCT04453306
Collaborator
(none)
80
1
2
91
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Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
80 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Double-blind Placebo-controlled Clinical TrialDouble-blind Placebo-controlled Clinical Trial
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.
Primary Purpose:
Treatment
Official Title:
Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome: a Double-blind Placebo-controlled Clinical Trial
Actual Study Start Date :
May 1, 2014
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: placebo

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.

Drug: Placebo
innocuous substance is coated in tablets in an independent laboratory

Experimental: intervention

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.

Drug: Topiramate
topiramate 25mg is coated in tablets in an independent laboratory

Outcome Measures

Primary Outcome Measures

  1. Change of Body Mass index (BMi) at 6 months [6 months]

    change of Body Mass index (BMi) in kg/m² from the baseline; weight and height will be combined to report BMI

  2. change in the modified Ferriman-Gallwey Hirsutism Score (mFG) at 6 months [6 months]

    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.

  3. Change of testosterone at 6 months [6 months]

    Change of testosterone (ng/mL) at 6 months from the baseline

  4. Change of glucose at 6 months [6 months]

    Change of glucose(mg/dL) at 6 months from the baseline

  5. Change of triglyceride at 6 months [6 months]

    Change of triglyceride (mg/dL) at 6 months from the baseline

  6. Change of High-density lipoprotein (HDL) at 6 months [6 months]

    Change of HDL cholesterol (mg/dL) at 6 months from the baseline

  7. Change of total cholesterol at 6 months [6 months]

    Change of total cholesterol (mg/dL) at 6 months from the baseline

  8. Change of Low-density lipoprotein (LDL) at 6 months [6 months]

    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

  9. Change of homeostatic model assessment (HOMA-IR) at 6 months [6 months]

    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.

  10. change in systolic blood pressure at 6 months [6 months]

    change in systolic blood pressure (mmHg) at 6 months from baseline.

  11. change in diastolic blood pressure at 6 months [6 months]

    change in diastolic blood pressure (mmHg) at 6 months from baseline.

Secondary Outcome Measures

  1. change of body composition at 6 months [6 months]

    Change in body composition evaluated through Dual-energy X-ray absorptiometry (DXA) from the baseline

  2. Change in anxiety score at 6 months [6 months]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 40 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • age between 18 and 40 years

  • diagnostic criteria for PCOS

  • overweight with a BMI ≥ 27 kg / m² associated with at least one comorbidity (hypertension, type 2 diabetes mellitus, dyslipidemia) or obesity with a BMI between 30 and 45 kg / m² with or without comorbidities

Exclusion Criteria:
  • severe systemic arterial hypertension (≥180 / 100 mmHg)

  • pregnant or lactating women

  • diabetics using sulfonylurea or insulin

  • any known allergy or intolerance to topiramate medication

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande Do Sul Brazil 90035-007

Sponsors and Collaborators

  • Hospital de Clinicas de Porto Alegre

Investigators

  • Principal Investigator: Poli Mara Spritzer, Federal University of Rio Grande do Sul

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier:
NCT04453306
Other Study ID Numbers:
  • 140228
First Posted:
Jul 1, 2020
Last Update Posted:
Jul 1, 2020
Last Verified:
Jun 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 1, 2020