Clinical trial NCT04881851: Effects of Inositol Alone or Associated With Alpha-lipoic Acid in Polycystic Ovary Syndrome Treatment
Official title: Effects of Inositol Alone or Associated With Alpha-lipoic Acid in Polycystic Ovary Syndrome Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Keywords: Inositol
alpha-lipoic acid
Lead sponsor: Universita di Verona
Sponsor class: OTHER
Collaborators: name: Laborest Italia SPA
First posted: 2021-05-11
Enrollment: 76
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blinded, three-armed RCT
Primary purpose: TREATMENT

Brief summary: The aim of this double-blinded, three-armed randomized controlled trial (RCT) is to evaluate the effects of a 6 months treatment with inositol alone or inositol associated with alpha-lipoic acid in women with polycystic ovary syndrome (PCOS).

The study population is composed of 90 women with PCOS (diagnosed according to the Rotterdam criteria). Subjects are randomized to one of the 3 arms of treatment (Inositol + alpha lipoic acid + folic acid vs inositol + folic acid vs folic acid alone).

At recruitment and after 6 months of treatment, the following data are collected:

* clinical data: height, weight, BMI, waist and hip circumference, blood pressure, Ferriman Gallwey Score, menstrual diary
* endocrine parameters (serum total and free testosterone levels, SHBG levels)
* metabolic profile: glycemia and insulinemia at fasting and after oral glucose tolerance test (OGTT), serum lipids
* insulin-sensitivity measured by the hyperinsulinemic-euglycemic clamp and surrogate indexes
* ovarian ultrasound data. Furthermore, ovulation is evaluated from the 2nd to the 6th month of the study through progesterone serial dosages on weekly urinary samples.

The primary outcome of the study is the serum free testosterone variation after 6 months of treatment. Secondary outcomes are the variations of lipid profile, ovarian morphology and insulin-sensitivity after 6 months and the number of ovulations occurring in the last 4 months of treatment.

Detailed description: The aim of this study is to evaluate the effects of a 6 months treatment with inositol, alone or associated with alpha-lipoic acid, in women with PCOS. This is a double blinded, three-armed RCT.

The study population is composed of 90 women with PCOS, recruited at the Department of Endocrinology and Metabolic Disease of Azienda Ospedaliera Universitaria Integrata (AOUI), Verona.

After recruitment, subjects are randomly assigned to one of the 3 arms of treatment (Inositol + alpha lipoic acid + folic acid vs inositol + folic acid vs folic acid alone). Randomisation is stratified by BMI category (3 categories 18\<BMI\<25, 25≥BMI\<30, 30≥BMI\<35 Kg/m2); randomisation list is generated by the statistical software Stata 13.1.

At baseline and after 6 months of treatment, the following data are collected:

* clinical examination: family and personal medical history, menstrual diary, physical examination including height, weight, waist and hip circumferences, blood pressure and hirsutism score (modified Ferriman-Gallwey score)
* total and free testosterone and sex hormone binding globulin (SHBG) blood levels, evaluated in the early follicular phase or after 3 months of amenorrhea
* metabolic profile: glycemia and insulinemia at fasting and after 2h OGTT, serum lipids (total cholesterol, HDL-cholesterol and triglycerides). Glycemia and insulinemia values during OGTT will be used to calculate surrogate indexes of insulin resistance
* insulin-sensitivity measured by the hyperinsulinemic-euglycemic clamp technique. Data obtained with this test will be normalized for lean mass, measured by bioelectrical impedance. The hyperinsulinemic-euglycemic clamp is repeated after 6 months of treatment only in subjects who are insulin-resistant at baseline (M-value \< 8.6 mg/kg min).
* Chronic inflammation markers (CRP)
* Ovarian ultrasound evaluation, including measurement of the 3 diameters for ovarian volume calculation, and follicle count. The ultrasound examination will be executed by a gynaecologist at the Department of Gynaecology and Obstetrics at AOUI, Verona.

Furthermore, all the study participants are subjected to:

* ovulation assessment by serial progesterone dosages on weekly urinary samples. Patients are given numbered urine beakers and are instructed to collect night urine weekly, starting at the 3rd month of treatment and until the end of the study (17 samples).
* monitoring visits after 2 and 4 months of treatment, to evaluate therapy compliance and possible adverse events.

  30 ml blood samples of the study participants will be preserved for 10 years. On these samples, further examinations will be considered if new important markers of PCOS will emerge in the future.

Eligibility criteria: Inclusion Criteria:

* female subjects
* age between 18 and 40 years old
* diagnosed with PCOS (according to the Rotterdam criteria)
* not use of possible interfering drugs in the 4 previous months
* written informed consent.

Exclusion Criteria:

* BMI ≥ 35 kg/m2
* acute illnesses
* chronic kidney or hepatic disease
* pregnant
* taking possible interfering drugs

Primary outcomes:
measure: Free testosterone variation
timeFrame: 6 months
Secondary outcomes:
measure: Insulin sensitivity variation
timeFrame: 6 months
measure: Lipid profile variation
timeFrame: 6 months
measure: Ovarian morphology variation
timeFrame: 6 months
measure: Number of ovulations in the last 4 months of treatment
timeFrame: 4 months
Other outcomes:
Locations:
city: Verona
country: Italy
facility: Endocrinology, Diabetes and Metabolism Section, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata of Verona
Study officials:
affiliation: Università degli studi di Verona
name: Paolo Moghetti, Professor
role: PRINCIPAL_INVESTIGATOR
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