Myo-inositol, D-chiro-inositol and Glucomannan in PCOS

August 1, 2018 updated by: Jacopo Troisi, University of Salerno

Effects of a Combined Treatment With Myo-inositol, D-chiro-inositol and Glucomannan in Women With PCOS

The aim of this study is to analyze the metabolic profiles in women with PCOS before and after 3 months of therapy with a combination of myo-inositol, D-chiro-inositol and glucomannan, and compare these data with a group of healthy control women.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  1. RATIONALE & BACKGROUND INFORMATION Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome and one of the most common female endocrine disorders, affecting 5-20% of women in reproductive age . Clinical expression is highly variable, but typically includes oligo-ovulation or anovulation, hyperandrogenism and polycystic ovaries . PCOS is associated with an increased risk of type 2 diabetes, cardiovascular events and endometrial cancer. Insulin Resistance (IR) plays a central role in approximately 70-80% of obese women and in 15-30% of lean women with PCOS, and represents the pathogenic link between metabolic and reproductive disorders in PCOS. According to recent guidelines, insulin-sensitizer drugs, like inositols, are the first-line therapy in women with metabolic abnormalities and irregular menstrual cycle with the purpose to improve fertility, whereas a lifestyle change with weight loss and physical activity is the first step in overweight and obese PCOS patients . Moreover, the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance. Metabolomic approach is used to better define the pathophysiology of PCOS and to describe how different therapies can modify metabolic profiles. Although the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance, the effect of inositols on the metabolomic profile of these women has not been described yet.
  2. STUDY GOALDS AND OBJECTIVES The aim of this study is to analyze the metabolic profiles in women with PCOS before and after 3 months of therapy with a combination of myo-inositol, D-chiro-inositol and glucomannan, and compare these data with a group of healthy control women.

  3. STUDY DESIGN The study is a prospective and observation. The inclusion criteria are: age between 18 and 35 years, overweight/obesity (BMI > 25 kg/m2), absence of any other acute intercurrent or chronic illness, a positive diagnosis of PCOS according to Rotterdam criteria. Exclusion criterion is using hormonal medications or drugs that affect insulin sensitivity (e.g., inositols or metformin) before enrollment.

    The use of myo-inositol (1.75 g), D-chiro-inositol (0.25 g) and glucomannan (4.0 g)/die must precede the recruitment of no more than 30 days. The decision to start treatment must have already been made before and independently of the start of the study. The use of inositol and glucomannan must take place according to the technical data sheet. In particular, myo-inositol (1.75 g), D-chiro-inositol (0.25 g) and glucomannan (4.0 g) are expected to be subdivided into two doses before main meals.

  4. METHODOLOGY 4.1 Admission visit (V0) Once the eligibility criteria have been checked, the investigator will inform the patient about the objectives of the study during the initial visit (V0) and obtain written informed consent form.

    The compilation of a clinical card includes general information, anamnesis, BMI, the characteristics of the menstrual cycle, the amount of menstrual loss, the degree of hirsutism according to the Ferriman-Gallwey index and the degree of acne in agreement to the Global evaluation scale proposed in 2002 by FDA.

    The investigator will collect from the clinical documentation available the baseline glycaemia, insulin, triglycerides, cholesterol values before the start of the treatment. Furthermore, information on the ultrasound picture will be collected in terms of ovary volumes and antral follicles.

    A sample of 2-3 ml of basal blood will be collected for metabolomic evaluations, using a BD vacutainer (Becton Dickinson, Oxfordshire, UK) blood collection red tube (with no additives). After centrifugation, the sample will immediately freeze to -80 °C until the time of analysis.

    The patient will then be invited to continue treatment with myo-inositol (1.75 g), D-chiro-inositol (0.25 g) and glucomannan (4 g) die and to show up for control after 90 days (V1).

    4.2 Follow-up visit 90th day (±15) after enrollment (V1) During the V1 the patient will be interviewed on the regular therapy and clinical symptoms, any adverse events and the course of the menstrual cycle.

    Furthermore, all patients will be re-evaluated regarding the anthropometric, biochemical and ultrasound parameters.

    At V1 a second blood sample of 2-3 ml will be collected with the same methods describe above.

    4.3 Biochemical and metabolomics samples analysis Blood concentration of glucose, insulin, triglycerides and cholesterol is evaluated for control subjects and for cases at baseline and after 3 months of treatment. HOMA-IR si also calculated. Ovary volumes and the antral follicles count were evaluated by a vaginal ultrasound performed by a trained gynecologist.

    Metabolome extraction, purification and derivatization is carried out with the MetaboPrep GC kit (Theoreo srl, Montecorvino Pugliano [SA], Italy) according to the manufacturer's instructions. Details regarding metabolite extraction and the overall analytical scheme, including QA/QC sample analyses, were reported in Troisi et al. (2017, 2018)

  5. Follow-Up Three months.

  6. Data Management and Statistical Analysis At the end of the treatments the data collection of all patients is scheduled and the introduction of the same, in coded or clear form, in a database (Excel for windows) appropriately structured to contain all the expected items. In order to comply with the privacy law, the sensitive nominal data will be appropriately replaced by the numerical codes assigned to each patient, so that from the simple consultation of the data it will not be possible to deduce any individual direct reference. Moreover, the only data that can be extracted from the database are related to aggregated sets to be published for scientific purposes.

    Data is reported as mean±standard deviation for continuous variables and number (percentage) for categorical variables.

    Statistical analysis are performed using Statistica software (StatSoft, Oklahoma, USA) and Minitab (Minitab Inc, Pennsylvania, USA). Normal distribution of data is verified using the Shapiro-Wilks test. Since the data are normally distributed, the investigators use one-way ANOVA with the Tukey post hoc test for inter-group comparisons. The alpha (ɑ) value is set to 0.05. Pearson's chi-squared test is used to determine differences among groups for the categorical variables.

    For multivariate data analysis, the chromatographic data are tabulated with one sample per row and one variable (metabolite) per column. Data pre-treatment consists of normalizing each metabolite peak area to that of the internal standard followed by generalized log transformation and data scaling by autoscaling (mean-centered and divide it by standard deviation of each variable). PLS-DA is performed using the statistical software package R (Foundation for Statistical Computing, Vienna, Austria). Class separation is achieved by PLS-DA, which is a supervised method that uses multivariate regression techniques to extract, via linear combinations of original variables (X), the information that can predict class membership (Y). PLS regression is performed using the plsr function included in the R pls package. Classification and cross-validation is performed using the corresponding wrapper function included in the caret package. A permutation test is performed to assess the significance of class discrimination. In each permutation, a PLS-DA model is built between the data (X) and the permuted class labels (Y) using the optimal number of components determined by cross validation for the model based on the original class assignment. Variable Importance in Projection (VIP) scores are calculated for each metabolite. The VIP score is a weighted sum of squares of the PLS loadings, taking into account the amount of explained Y-variation in each dimension. The highest scoring VIP metabolites are compared in terms of fold changes (FC). FC is the ratio of the mean abundances between any two classes and is a measure describing how much a quantity changes going from an initial to a final value.

    The metabolic pathways are constructed using MetScape application of the software Cytoscape.

  7. Expected Outcomes of the Study The goal of this pilot study is to identify a complex network of serum molecules that appear to be correlated with PCOS, and with a combined treatment with inositols and glucomannan.
  8. Duration of the Project 24 months

Study Type

Observational

Enrollment (Actual)

120

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 33 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Young women with a PCOS diagnosis without intercurrent chronic illness and a matched healthy population.

Description

Inclusion Criteria:

  • overweight/obesity (BMI > 25 kg/m2);
  • absence of any other acute intercurrent or chronic illness;
  • a positive diagnosis of PCOS according to Rotterdam criteria.

Exclusion Criteria:

  • Use of hormonal medications or drugs that affect insulin sensitivity (e.g., inositols or metformin) before enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Controls
Healthy subjects
Other: Serum Metabolomics profiling
Untargeted serum metabolomics profiling
Case
PCOS affected subjects
Other: Serum Metabolomics profiling
Untargeted serum metabolomics profiling

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Untargeted serum metabolomics profiling
Time Frame: 6 months
Identify a complex network of serum molecules that appear to be correlated with PCOS, and with a combined treatment with inositols and glucomannan.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Salerno

Collaborators

Theoreo Srl

Investigators

  • Principal Investigator: Jacopo Troisi, CEO, Theoreo srl

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 10, 2016

Primary Completion (Actual)

September 10, 2016

Study Completion (Actual)

July 31, 2017

Study Registration Dates

First Submitted

July 24, 2018

First Submitted That Met QC Criteria

July 31, 2018

First Posted (Actual)

August 1, 2018

Study Record Updates

Last Update Posted (Actual)

August 3, 2018

Last Update Submitted That Met QC Criteria

August 1, 2018

Last Verified

August 1, 2018

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • PCOS-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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