MYOPK: Interest of Myo-inositol Supplementation in Women With Polycystic Ovarian Syndrome

Sponsor

University Hospital, Lille (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03059173

Collaborator

Ministry of Health, France (Other), Laboratoires Besins International (Industry)

276

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The main objective will be to check if MyoInositol (MYO) reduces the total resistance rate to Clomiphene Citrate (CC). For this, our study will be controlled, randomized and double blinded. It will include patients with PCOS (polycystic ovary syndrome, defined by the Rotterdam criteria) who wish to become pregnant and are eligible to simple ovulation induction by CC. Half of them will receive MYO + levomefolic acid (5-MTHF) in addition to the CC, while the other half will receive a placebo containing only 5-MTHF in addition to the CC. The MYO supplementation will be initiated at least one month before taking CC and will be continued throughout this treatment until pregnancy or before switching to another type of treatment for ovulation induction if no pregnancy is obtained after 6 ovulatory cycles.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome Reproductive Medicine	Dietary Supplement: Myo-Inositol + Levomefolic acid Drug: Clomiphene Citrate Dietary Supplement: placebo	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

276 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Interest of Myo-inositol Supplementation in Women With Polycystic Ovarian Syndrome During Induction of Ovulation With Clomiphene Citrate

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Myo-Inositol + Levomefolic acid The experimental group will receive the dietary supplement: 4 g of MYO + 0.736 mg of 5-MTHF, glucosamine salts per day per os (in 2 bags per day) in addition to the standard therapy (Clomiphene Citrate).	Dietary Supplement: Myo-Inositol + Levomefolic acid Dietary supplement Gynositol® MTHF containing myo-inositol (4 g) and Levomefolic acid on glucosamine salts(0.736 mg) in a same bags Supplementation started on average one month before treatment with Clomiphene citrate and continued throughout cycles of Clomiphene citrate (maximum 9 cycles). Treatment will be delivered during ultrasound visit at D12 of each cycle. Other Names: Myo + [6S]-5-MethylTetrahydrofolate(5-MTHF) ou Gynositol (R) Drug: Clomiphene Citrate Clomiphene citrate 50 mg. taking D2 to D6 of each cycle (maximum 9 cycles). Treatment will be delivered during ultrasound visit at D12 of each cycle and the dose will be increased if necessary.
Placebo Comparator: Placebo The control group will receive the standard therapy ( Clomiphene Citrate) and a placebo containing only 0.736 mg of 5-MTHF, glucosamine salts	Drug: Clomiphene Citrate Clomiphene citrate 50 mg. taking D2 to D6 of each cycle (maximum 9 cycles). Treatment will be delivered during ultrasound visit at D12 of each cycle and the dose will be increased if necessary. Dietary Supplement: placebo a placebo containing only 0.736 mg of 5-MTHF, glucosamine salts

Arm

Intervention/Treatment

Experimental: Myo-Inositol + Levomefolic acid

The experimental group will receive the dietary supplement: 4 g of MYO + 0.736 mg of 5-MTHF, glucosamine salts per day per os (in 2 bags per day) in addition to the standard therapy (Clomiphene Citrate).

Dietary Supplement: Myo-Inositol + Levomefolic acid

Dietary supplement Gynositol® MTHF containing myo-inositol (4 g) and Levomefolic acid on glucosamine salts(0.736 mg) in a same bags Supplementation started on average one month before treatment with Clomiphene citrate and continued throughout cycles of Clomiphene citrate (maximum 9 cycles). Treatment will be delivered during ultrasound visit at D12 of each cycle.

Other Names:

Myo + [6S]-5-MethylTetrahydrofolate(5-MTHF) ou Gynositol (R)

Drug: Clomiphene Citrate

Clomiphene citrate 50 mg. taking D2 to D6 of each cycle (maximum 9 cycles). Treatment will be delivered during ultrasound visit at D12 of each cycle and the dose will be increased if necessary.

Placebo Comparator: Placebo

The control group will receive the standard therapy ( Clomiphene Citrate) and a placebo containing only 0.736 mg of 5-MTHF, glucosamine salts

Drug: Clomiphene Citrate

Clomiphene citrate 50 mg. taking D2 to D6 of each cycle (maximum 9 cycles). Treatment will be delivered during ultrasound visit at D12 of each cycle and the dose will be increased if necessary.

Dietary Supplement: placebo

a placebo containing only 0.736 mg of 5-MTHF, glucosamine salts

Outcome Measures

Primary Outcome Measures

Total resistance rate under CC for ovulation induction in patients with PCOS. [At each cycle during 4 months]
The total resistance to CC is defined by failure to ovulate at least one time during 4 subsequent cycles in women requiring 150 mg/day from D2 to D6.

Secondary Outcome Measures

Rate of responders (i.e., 100% cycles with ovulation and/or occurrence of a pregnancy) at doses of 50 and 100mg of CC [At each cycle during one year]
Rate of drop out [at each cycle during one year]
Cumulative incidence of clinical pregnancy (cardiac activity on ultrasound at 6 weeks of amenorrhea) [During one year]
Rate of patients switched to a 2nd line treatment with exogenous gonadotropins over the whole period of the study [At each cycle during one year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Wishing pregnancy,
Having PCOS defined by the Rotterdam criteria: high antral follicle count (AFC) (> 19 per ovary) and/or a disorder of the cycle and/or hyperandrogenism (at least two of the three criteria),
Having never been treated with CC (or previous treatment with CC interrupted for > 3 months).
Having received complete information and having signed consent.
Covered by social security

Exclusion Criteria:

Intolerance to CC in previous treatment,
BMI > 35,
Other associated cause of oligoanovulation requiring specific treatment (eg., Hyperprolactinemia or functional hypothalamic anovulation),
Ongoing pregnancy at the time of CC initiation,
Other male or female cause of hypo-fertility,
History of ovarian drilling,
Negative rubella serology.