Myo-inositol Versus Clomiphene Citrate in PCOS

Myo-inositol Versus Clomiphene Citrate as First Line Treatment for Ovulation Induction in PCOS

Specific aim: To compare inositol and the golden standard first line treatment of ovulation induction, namely clomiphene citrate.

Study Overview

• Status: Terminated
• Conditions: Polycystic Ovary Syndrome; Ovulation Induction; Clomiphene; Inositol
• Intervention / Treatment: Drug: Myo-inositol; Drug: Clomiphene Citrate

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Frank Vandekerckhove, Prof.; Phone Number: 0032 9 332 54 73; Email: frank.vandekerckhove@uzgent.be
• Study Contact Backup: Name: Rebecca De Beir, Msc.; Phone Number: 0032 9 332 37 57; Email: rebecca.debeir@uzgent.be

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • University Hospital

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:

• Rotterdam criteria for PCOS (cf. the recent ESHRE guidelines): at least 2 out of 3 criteria should be fulfilled: irregular cycle (shorter than 21 days or longer than 35 days); clinical (modified Ferriman-Gallwey score ≥ 6) or biochemical signs (elevated free testosterone) of hyperandrogenism (www.eshre.eu/Guidelines-and- Legal/Guidelines/Polycystic-Ovary-Syndrome.aspx); PCO ovaries on ultrasound (www.eshre.eu/Guidelines-and- Legal/Guidelines/Polycystic-Ovary-Syndrome.aspx): multiple small cysts (≥ 20 per ovary and/or an ovarian volume ≥ 10 ml, measured with a probe >8 MHz) in both ovaries.
• A first treatment cycle, possibly combined with intra uterine insemination (IUI) and this for (one of) the following reasons: mild male factor (as defined by each local center) endometriosis AFS score 1 or 2
• Use of own or donor sperm.

Exclusion Criteria:

• Tubal factors
• Uterine factors
• Endometriosis AFS score 3 or 4
• Moderate to severe male factor (as defined by each local center)
• BMI > 35

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inositol group; Myo-inositol 4000 mg Dosing: 2 x 1 bag per day, per os (subjects can take myo-inositol during the meal but it is not obliged) during 3 consecutive treatment cycles.	Drug: Myo-inositol; 2 x 1 bag per day, per os (subjects can take myo-inositol during the meal but it is not obliged).
Active Comparator: Clomiphene citrate group; Each tablet contains 50 mg of clomiphene citrate Dosing: 1 tablet per day, per os, from cycle day 3 until 7 (extremes included), stepping up until a maximum dose of 3 tablets per day for 5 consecutive days during 3 consecutive treatment cycles.	Drug: Clomiphene Citrate; Each tablet contains 50 mg of clomiphene citrate which means 33,9 mg of clomiphene. Other constituents are sucrose, lactose monohydrate, corn starch, pregelatinized starch, yellow iron oxide (E172) and magnesium stearate (E470b). Dosing: 1 tablet per day from cycle day 3 until 7 (extremes included), stepping up until a maximum dose of 3 tablets per day for 5 consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of cumulative ongoing pregnancy (a pregnancy diagnosed by ultrasonic visualisation of one or more gestational sacs with fetal heart beat) after 3 treatment cycles with inositol versus clomiphene citrate for ovulation induction.	Recently, a meta-analysis on the use of inositol in PCOS was published. This study showed that inositol leads to a more regular menstrual cycle and recovery of ovarian function. Less data are present on pregnancy rates. No RCT was found on the comparison between inositol and the golden standard first line treatment of ovulation induction, namely clomiphene citrate. Another advantage of inositol is that it doesn't have side effects compared to metformin and that there is no elevated risk on multiple pregnancies, which is the case with clomiphene citrate.	At 7 - 8 gestational weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of potential adverse events	The potential adverse events will be measured to determine whether the compliance for the patient is acceptable.	During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks)
The occurrence of ovulation	The occurence of ovulation will be measured to determine whether the compliance for the patient is acceptable.	During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks)
The number of cancelled treatment cycles	The number of cancelled treatment cycles will be measured to determine whether the compliance for the patient is acceptable.	During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks)
The number of multiple pregnancies	The number of multiple pregnancies will be measured to determine whether the compliance for the patient is acceptable.	During 3 consecutive treatment cycles (each treatment cycle is up to 5 weeks)

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: University Hospital, Antwerp; AZ Jan Palfijn Gent; Gedeon Richter Plc.; Our Lady of Lourdes Hospital Waregem

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2020
• Primary Completion (Actual): April 20, 2021
• Study Completion (Actual): January 31, 2022

Study Registration Dates

• First Submitted: February 12, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 13, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Micronutrients; Hormone Antagonists; Vitamins; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Vitamin B Complex; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene; Enclomiphene; Zuclomiphene; Inositol
• Other Study ID Numbers: 2018-004604-20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No