Treatment of Obesity With Topiramate in Patients With Polycystic Ovary Syndrome

Obesity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04453306
• Other study ID #: 140228
• Status: Recruiting
• Phase: Phase 4
• Start date: May 2014
• Est. completion date: December 2021

Study information

• Verified date: June 2020
• Source: Hospital de Clinicas de Porto Alegre
• Contact: Lucas Marchesan
• Phone: +55 51 993873838
• Email: lucas.iuk[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperandrogenism
• Obesity
• Polycystic Ovary Syndrome
• Syndrome

Intervention

Drug:
• Topiramate
topiramate 25mg is coated in tablets in an independent laboratory
• Placebo
innocuous substance is coated in tablets in an independent laboratory

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Change of testosterone at 6 months	Change of testosterone (ng/mL) at 6 months from the baseline	6 months
Primary	Change of glucose at 6 months	Change of glucose(mg/dL) at 6 months from the baseline	6 months
Primary	Change of triglyceride at 6 months	Change of triglyceride (mg/dL) at 6 months from the baseline	6 months
Primary	Change of High-density lipoprotein (HDL) at 6 months	Change of HDL cholesterol (mg/dL) at 6 months from the baseline	6 months
Primary	Change of total cholesterol at 6 months	Change of total cholesterol (mg/dL) at 6 months from the baseline	6 months
Primary	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
Primary	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
Primary	change in systolic blood pressure at 6 months	change in systolic blood pressure (mmHg) at 6 months from baseline.	6 months
Primary	change in diastolic blood pressure at 6 months	change in diastolic blood pressure (mmHg) at 6 months from baseline.	6 months
Secondary	change of body composition at 6 months	Change in body composition evaluated through Dual-energy X-ray absorptiometry (DXA) from the baseline	6 months
Secondary	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