Effect of ALA Combined With Letrozole on Polycystic Ovary Syndrome Clinical Outcome in Infertile Females

NCT06418347 | Recruiting Phase 3 DMC

• 1 other identifier: ALA on PCOS
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief Summary

This research study aims to investigate the effect of adding Alpha lipoic acid (ALA) supplement to letrozole treatment in infertile women with polycystic ovary syndrome (PCOS). The study will include 150 PCOS participants seeking fertility treatment. They will be randomly divided into two groups - control and intervention. Both groups will receive standard PCOS care including lifestyle counseling. The control group will be treated with letrozole only. The dose will start at (2.5 mg) for 5 days and can increase up to (7.5 mg) based on response. The intervention group will take ALA supplements along with letrozole treatment. ALA tablets (600mg) will be given three times daily starting from day 3 of the menstrual cycle till human chorionic gonadotropin (HCG) injection day. Letrozole dose for the intervention group will also follow the same incremental protocol as the control group. Patient monitoring will involve trans-vaginal ultrasound scans on certain cycle days to check follicle growth and the thickness of uterus lining. Once a follicle reaches 18mm in size, an intramuscular HCG injection will be given. Couples will be asked to have intercourse 36 hours after the injection. Pregnancy will be tested two weeks later if menstruation does not occur. Metabolic, hormonal, and ultrasound parameters will be recorded at baseline and follow-ups. All adverse effects of the treatment will be noted. The study period will be a maximum of 3 treatment cycles or untill pregnancy is achieved. Outcome measures include ovulation and pregnancy rates. The effect of ALA on metabolic parameters (fasting glucose, fasting insulin, BMI and HOMA-IR), hormone levels (mid-luteal progesterone and serum estradiol), and follicular growth will also be assessed. Proper sample size and randomization methods will be followed. A Statistical analysis of collected data will help determine if ALA has additional benefits when combined with letrozole for PCOS fertility treatment. Finally, the results will be statistically analyzed. Statistical analysis will be done using the SPSS statistical software package.

Conditions

Polycystic Ovary Syndrome; Infertility, Female

Keywords

PCOS; ALA; Letrozole; Infertility; Ovulation rate

Outcome Measures

Primary Outcomes (1)

• The primary outcome is cumulative ovulation rate

  which is defined as the proportion of cycles in which ovulation occurred in the whole follow-up period.

  1 year

Secondary Outcomes (8)

• The clinical pregnancy rate

  1 year

• BMI in kg/m^2

  1 year

• HOMA-IR

  1 year

• serum estradiol

  1 year

• mid-luteal progesterone

  1 year

Study Arms (2)

Control

OTHER

This group will include 75 PCOS participants who will receive the standard treatment letrozole and the other commonly provided PCOS care (lifestyle modification, diet and exercise education, any other non-pharmacological method of management) according to the PCOS guidelines .Treatment with letrozole will begin after the baseline visit and for three cycles.

Drug: Letrozole

Intervention

EXPERIMENTAL

this will include 75 PCOS participants who will receive the standard treatment as letrozole with the same schedule of the control group and the other commonly provided PCOS care as previously described in addition to ALA, (Thiotacid®, EVAPHARMA, Egypt) in a dose of one tablet "600 mg" three times per day Each patient in the test group will start the ALA from day 3 of the menstrual period then daily until the day of human chorionic gonadotropin (HCG) injection

Drug: Alpha lipoic acid; Drug: Letrozole

Interventions

Alpha lipoic acid DRUG

Alpha-lipoic acid (ALA), also known as 1,2-dithiolane-3-pentanoic acid or thioctic acid, is found in the mitochondria. It acts as an enzymatic cofactor for various enzymes in the Kreb's cycle. ALA has many beneficial properties making it a potential candidate for various clinical disorders. It is considered the universal or "ideal" antioxidant as it is both water-soluble and fat-soluble facilitating its passage across membran. ALA has direct as well as indirect anti-inflammatory effects. Being a potent antioxidant leads to a reduction in oxidative stress which in turn reduces inflammation, meaning ALA indirectly has anti-inflammatory effects. To add to ALA's benefits, it has anti-inflammatory properties that are independent of its antioxidant effects.

Also known as: ALA

Intervention

Letrozole DRUG

Letrozole is an aromatase inhibitor that controls the conversion of androgen to estrogen and increases ovarian androgens. The administration of letrozole in the follicular phase removes the effect of negative estrogen feedback on the pituitary and hypothalamus, thus increasing the gonadotropins\]. When Letrozole blocks estrogen production, it encourages the body to produce more follicle-stimulating hormone (FSH).The additional FSH stimulates egg development and increases the likelihood of ovulation. Kar, S. Found that letrozole has excellent pregnancy rates compared to clomiphene citrate, Letrozole should be considered at par with clomiphene citrate as first-line drug for ovulation induction in infertile PCOS women.

Control; Intervention

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female patient aged 18-35
• Willing to conceive
• PCOS, diagnosed according to the revised 2003 Rotterdam consensus criteria. " Oligo- or anovulation secondary to PCOS and at least one of the remaining two criteria: hyperandrogenism or polycystic ovarian morphology on ultrasound .
• Anovulation and/or infertility ≥ 1 year.
• At least one patent fallopian tube
• Normal uterine cavity
• Male partner with sperm concentration of at least 14 million/mL in at least one ejaculate.

You may not qualify if:

• Other causes for the infertility (male factor, tubal factor).
• Intake of hormonal or other drugs that can potentially influence the ovulation.
• Causes of anovulation or hyperandrogenism other than PCOS such as uncontrolled thyroid dysfunction or hyperprolactinemia.
• Contraindication to pregnancy
• Myo-inositol use \< 3 months prior to study enrollment
• Concomitant metformin use. Previous use is allowed with last use at least 6 weeks prior to randomization.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (2)

Ain shams university

Cairo, Cairo Governorate, 11566, Egypt

RECRUITING

Ain shams university

Cairo, Cairo Governorate, 11566, Egypt

RECRUITING

Related Publications (3)

• Fruzzetti F, Benelli E, Fidecicchi T, Tonacchera M. Clinical and Metabolic Effects of Alpha-Lipoic Acid Associated with Two Different Doses of Myo-Inositol in Women with Polycystic Ovary Syndrome. Int J Endocrinol. 2020 Mar 19;2020:2901393. doi: 10.1155/2020/2901393. eCollection 2020.

  PMID: 32256570 BACKGROUND

• Genazzani AD, Shefer K, Della Casa D, Prati A, Napolitano A, Manzo A, Despini G, Simoncini T. Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients. J Endocrinol Invest. 2018 May;41(5):583-590. doi: 10.1007/s40618-017-0782-z. Epub 2017 Oct 31.

  PMID: 29090431 BACKGROUND

• Masharani U, Gjerde C, Evans JL, Youngren JF, Goldfine ID. Effects of controlled-release alpha lipoic acid in lean, nondiabetic patients with polycystic ovary syndrome. J Diabetes Sci Technol. 2010 Mar 1;4(2):359-64. doi: 10.1177/193229681000400218.

  PMID: 20307398 BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility, Female; Infertility

Interventions

Thioctic Acid; Letrozole

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Carboxylic Acids; Organic Chemicals; Thiophenes; Sulfur Compounds; Coenzymes; Enzymes and Coenzymes; Fatty Acids; Lipids; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Muoaz A. Sallam, Teaching assistance

CONTACT

+0201102174081; Moaaz.ahmed22@pharma.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: May 17, 2024
• Study Start: April 1, 2024
• Primary Completion: November 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 24, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

EG (2)