Clomiphene Plus N-acetyl Cysteine for Induction of Ovulation in Newly Diagnosed Pcos. (NACIPCOS)

Clomiphene Citrate Plus N-acetyl Cysteine Versus Clomiphene Citrate for Induction of Ovulation in Women With Newly Diagnosed Polycystic Ovary Syndrome: a Randomized Double-blind Controlled Trial

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting approximately 6-10% of women of reproductive age. Anovulation, infertility and hyperandrogenism often co-exist with hyperinsulinaemia and insulin resistance .

Clomiphene citrate remains the standard drug for induction or augmentation of ovulation. However, it is not equally effective in all situations, and therefore it may require additional expensive drugs such as N-acetyl cysteine, as an antioxidant, has been suggested as an adjuvant in clomiphene-resistant cases .NAC may also improve the circulating level of insulin and insulin sensitivity in hyperinsulinaemic women with PCOS, and may be useful for the treatment of insulin resistance by ameliorating the homocysteine and lipid profile in PCOS .

Study Overview

• Status: Completed
• Conditions: PCOS
• Intervention / Treatment: Drug: NAC

Detailed Description

NAC has been used effectively as an adjuvant to clomiphene citrate (CC) for ovulation induction in CC-resistant women with PCOS .

Because it is an insulin sensitizer, NAC was proposed as an adjuvant to clomiphene citrate for ovulation induction in patients with polycystic ovary syndrome who are resistant to clomiphene citrate. Encouraging results in those patients stimulated us to investigate whether adding NAC to the standard treatment with CC results in a higher ovulation rate, higher pregnancy rate, and less CC resistance in women with newly diagnosed polycystic ovary syndrome using a randomized, double-blind, controlled study.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• PCOS diagnosed by Rotterdam's criteria

Exclusion Criteria:

• previous induction of ovulation male factoe infertility tubal factor infertility uterine factor infertility

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N-acetyl cystien and clomiphen citrate; N-acetyl cystien and clomiphen citrate,in induction of ovulation in newly diagnosed PCOS,1-2gm schats of NAC PLUS 100 mg of cc in the therd day of the cycle till day 8,with monitoring of follicular growth usin ultrasonography.HCG is giving to trigger of ovulation fo follicular size 18mm or more.	Drug: NAC; NAC 2gm plus cc 100mg from 3rd day of the cycle till day 8 with u/s follow up of the follicular growth.; Other Names: N-acetyl cystien
Placebo Comparator: Clomiphen citrate and placebo; CC plus placebo compared to cc and NAC in induction of ovulation in PCOS new cases.	Drug: NAC; NAC 2gm plus cc 100mg from 3rd day of the cycle till day 8 with u/s follow up of the follicular growth.; Other Names: N-acetyl cystien
No Intervention: N-acetyl cystien; In addition to the CC, each patient was selected randomly to receive either NAC (Sedico, Cairo, ARE), in a dose of 1.2 g/d orally, or a placebo (sugar) of the same volume twice daily from day 3 until day 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ovulation rate	Clomiphene citrate, 100 mg, was given from day 3 until day 7. In addition to the CC, each patient was selected randomly to receive either NAC (Sedico, Cairo, ARE), in a dose of 1.2 g/d orally, or a placebo (sugar) of the same volume twice daily from day 3 until day 7. Monitoring of the cycle will involve transvaginal determination of the mean follicular diameter and measurement of serum E2 levels. Monitoring intervals will be determined by patient response.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
include PR, number of follicles of ≥ 18 mm, the serum E2 concentration, serum P, and endometrial thickness	Clomiphene citrate, 100 mg, was given from day 3 until day 7. In addition to the CC, each patient was selected randomly to receive either NAC (Sedico, Cairo, ARE), in a dose of 1.2 g/d orally, or a placebo (sugar) of the same volume twice daily from day 3 until day 7. Monitoring of the cycle will involve transvaginal determination of the mean follicular diameter and measurement of serum E2 levels. Monitoring intervals will be determined by patient response. Human chorionic gonadotropin will be given when at least one follicle measured 18 mm and the E2 level had increased. Timed intercourse will be advised 24-36 hours after hCG injection. A serum P level will be checked on cycle days 21-22. A serum hCG level will be determined 14 days after hCG injection if menses had not yet occurred. Pregnancy will be defined as an increase in the serum hCG level on serial determinations at least 2 days apart.	2 years

Collaborators and Investigators

• Sponsor: Woman's Health University Hospital, Egypt
• Investigators: Principal Investigator: Alaa M Ismail, M D, Woman's Health University Hospital, Egypt

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 22, 2013
• First Submitted That Met QC Criteria: July 5, 2013
• First Posted (Estimate): July 11, 2013

Study Record Updates

• Last Update Posted (Actual): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: PCOS,; NAC,; OVULATION INDUCTION,; CLOMOPHEN CITRATE
• Other Study ID Numbers: ccpnacinovi

Drug and device information, study documents

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