Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome

Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome: a Double-blind Placebo-controlled Clinical Trial

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

Study Overview

• Status: Unknown
• Conditions: Obesity; Polycystic Ovary Syndrome; Hyperandrogenism
• Intervention / Treatment: Drug: Placebo; Drug: Topiramate

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 Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lucas Marchesan; Phone Number: +55 51 993873838; Email: lucas.iuk@gmail.com

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-007
      • Recruiting
      • Hospital de Clinicas de Porto Alegre
      • Contact: Lucas B Marchesan; Phone Number: +55 51 993873838; Email: lucas.iuk@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Body Mass index (BMi) at 6 months	change of Body Mass index (BMi) in kg/m² from the baseline; weight and height will be combined to report BMI	6 months
change in the modified Ferriman-Gallwey Hirsutism Score (mFG) at 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.	6 months
Change of testosterone at 6 months	Change of testosterone (ng/mL) at 6 months from the baseline	6 months
Change of glucose at 6 months	Change of glucose(mg/dL) at 6 months from the baseline	6 months
Change of triglyceride at 6 months	Change of triglyceride (mg/dL) at 6 months from the baseline	6 months
Change of High-density lipoprotein (HDL) at 6 months	Change of HDL cholesterol (mg/dL) at 6 months from the baseline	6 months
Change of total cholesterol at 6 months	Change of total cholesterol (mg/dL) at 6 months from the baseline	6 months
Change of Low-density lipoprotein (LDL) at 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	6 months
Change of homeostatic model assessment (HOMA-IR) at 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.	6 months
change in systolic blood pressure at 6 months	change in systolic blood pressure (mmHg) at 6 months from baseline.	6 months
change in diastolic blood pressure at 6 months	change in diastolic blood pressure (mmHg) at 6 months from baseline.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of body composition at 6 months	Change in body composition evaluated through Dual-energy X-ray absorptiometry (DXA) from the baseline	6 months
Change in anxiety score at 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.	6 months

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Poli Mara Spritzer, Federal University of Rio Grande do Sul

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: June 23, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): July 1, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 26, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Polycystic Ovary Syndrome; Hyperandrogenism; Syndrome; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: 140228

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• 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