Effect of NAE on Polycystic Ovarian Syndrome (PCOS)

NCT07603505 | Recruiting Phase 1

• 2 other identifiers: NAE-PCOS-2024NO.F.2-81/2024-GENL/101/JPMC
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

Polycystic Ovarian Syndrome (PCOS) is a multifaceted endocrine metabolic condition impacting about 5-10% of women throughout their reproductive lifespan. It is influenced by neuroendocrine dysfunction, insulin resistance, chronic low-grade inflammation, and ovarian oxidative stress. Existing medications, including metformin, clomiphene citrate, and anti-androgens, provide only limited advantages and are frequently restricted by side effects such as gastrointestinal intolerance, teratogenic risks, and weight gain. NAE (family Lamiaceae) is a fragrant perennial herb indigenous to the Himalayan and sub-Himalayan areas of Pakistan and Afghanistan. Phytochemical profiling of this plant has revealed high concentrations of flavonoids (luteolin, apigenin, quercetin), phenolic acids (rosmarinic and caffeic acid), terpenoids (nepetalactones), and glycosides. In a preclinical study lasting 30 days that involved Letrozole induced PCOS in Albino Wistar rats, the oral delivery of crude extract (350 and 500 mg/kg) and its methanol/butanol fractions (64 mg/kg; 12.5mg/kg) significantly restored estrous cyclicity, decreased serum LH and testosterone levels, normalized the LH/FSH ratio, enhanced insulin sensitivity (reduced HOMA IR), corrected dyslipidaemia, and reversed ovarian histopathological alterations. Molecular analysis by qRT PCR showed upregulation of IL 4 and downregulation of AR, CYP-17, TLR4, TNF α, and NF κB. Based on this multi targeted preclinical efficacy and a favourable safety profile, this clinical trial will assess the safety and effectiveness of a standardised NAE in women with PCOS, compared to metformin and combination therapy over 4 months.

Conditions

Polycystic Ovarian Syndrome (PCOS); Infertility; Metabolic Disorders

Keywords

Polycystic Ovarian Syndrome (PCOS); NAE extract; metabolic disorder; herbal medicine; insulin resistance; metformin

Outcome Measures

Primary Outcomes (1)

• Menstrual Cycle Normalisation

  Regular ovulatory cycles lasting from 21 to 35 days achieved after finishing 4 months of treatment. Cycle regularity is recorded through menstrual diaries maintained by participants and validated by transvaginal ultrasound, where ovulation is recognized by the presence of a dominant follicle (≥18 mm) that later either collapses or vanishes, with or without free fluid present in the pouch of Douglas.

  Baseline to 4 months

Secondary Outcomes (7)

• Body Weight Changes

  Baseline and 4 months

• Serum Follicle-Stimulating Hormone (FSH) Levels

  Baseline and 4 months

• Serum Luteinizing Hormone (LH) Levels

  Baseline and 4 months

• Serum Testosterone Levels

  Baseline and 4 months

• Glycated Hemoglobin (HbA1c) Level

  Baseline and 4 months

Other Outcomes (1)

• Assessment of quality of life via Polycystic Ovary Syndrome Quality of Life scale (PCOSQOL)

  Baseline and 4 months

Study Arms (3)

NAE treated group

EXPERIMENTAL

NAE 500 mg twice daily for 4 months in PCOS patients

Drug: Herbal Formulation

Metformin XR treated group

ACTIVE COMPARATOR

Metformin XR 750 mg twice daily for 4 months in PCOS patients

Drug: Metformin XR

Adjunct Group

EXPERIMENTAL

NAE 500 mg and Metformin XR 750 mg twice daily for 4 months in PCOS patients

Drug: Metformin 750 mg and herbal formulation 500 mg

Interventions

Herbal Formulation DRUG

NAE 500 mg twice daily for 4 months in PCOS patients

NAE treated group

Metformin XR DRUG

Metformin XR 750 mg twice daily for 4 months in PCOS patients

Metformin XR treated group

Metformin 750 mg and herbal formulation 500 mg DRUG

NAE 500 mg and Metformin XR 750 mg twice daily for 4 months in PCOS patients

Adjunct Group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Female subjects in reproductive age (18-40 years)
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female subjects of reproductive age (18-40 years).
• Subjects with a diagnosis of polycystic ovary syndrome (PCOS) confirmed by clinician diagnostic criteria (Rotterdam criteria).
• Subjects with insulin resistance defined as HOMA-IR \> 2.00.

You may not qualify if:

• Pregnant or lactating women.
• Subjects with known Cushing's syndrome.
• Subjects with late-onset congenital adrenal hyperplasia.
• Subjects with androgen-secreting tumors.
• Subjects with uncontrolled thyroid disease.
• Subjects with hyperprolactinemia.
• Subjects with diabetes mellitus.
• Subjects with uncontrolled hypertension.
• Subjects with other cardiovascular diseases.
• Subjects with acute or chronic infections.
• Subjects with any known malignancy.
• Subjects with impaired renal function (serum creatinine \> 1.5 × ULN).
• Subjects with impaired liver function (serum ALT ≥ 2.5 × ULN).

Sponsors & Collaborators

• Jinnah Sindh Medical University: lead

Study Sites (1)

Jinnah Postgraduate Medical Centre

Karachi, Sindh, Pakistan

RECRUITING

Related Publications (13)

• Hosseini S, Shabani F, Nayebzadeh M, Asadi F, Kabiranaraki Y, Asadpour M, Golavar Y, Asadi S, Etezadi A. Neutrophils and NETosis in polycystic ovary syndrome: unraveling the immuno-metabolic thromboinflammatory axis. Eur J Med Res. 2026 Jan 27;31(1):331. doi: 10.1186/s40001-026-03927-7.

  PMID: 41593809 BACKGROUND

• Houston EJ, Templeman NM. Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS. J Endocrinol. 2025 Mar 12;265(2):e240269. doi: 10.1530/JOE-24-0269. Print 2025 May 1.

  PMID: 40013621 BACKGROUND

• Zeber-Lubecka N, Ciebiera M, Hennig EE. Polycystic Ovary Syndrome and Oxidative Stress-From Bench to Bedside. Int J Mol Sci. 2023 Sep 15;24(18):14126. doi: 10.3390/ijms241814126.

  PMID: 37762427 BACKGROUND

• Zhao W, Li M, Jia C, Ali I, Chen L. Anti-inflammatory effect of a pimarane diterpenoid isolated from Nepeta adenophyta Hedge based on a network analysis approach and experimental assessment. Front Pharmacol. 2025 Dec 18;16:1652902. doi: 10.3389/fphar.2025.1652902. eCollection 2025.

  PMID: 41487516 BACKGROUND

• Dashti S, Ashouri A, Bahri N. Herbal compounds in the treatment of polycystic ovary syndrome: an updated systematic review. J Ovarian Res. 2026 Feb 27;19(1):132. doi: 10.1186/s13048-026-02030-z.

  PMID: 41761211 BACKGROUND

• Li C, Chen L, Zhao Y, Chen S, Fu L, Jiang Y, Gao S, Liu Z, Wang F, Zhu X, Rao J, Zhang J, Zhou X. Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model. Gene. 2017 Jan 20;598:20-26. doi: 10.1016/j.gene.2016.10.033. Epub 2016 Oct 21.

  PMID: 27777110 BACKGROUND

• Sharma A, Cooper R, Bhardwaj G, Cannoo DS. The genus Nepeta: Traditional uses, phytochemicals and pharmacological properties. J Ethnopharmacol. 2021 Mar 25;268:113679. doi: 10.1016/j.jep.2020.113679. Epub 2020 Dec 8.

  PMID: 33307050 BACKGROUND

• Wu X, Yi W, Liu X. Precision Targeted Therapy for PCOS: Emerging Drugs, Translational Challenges, and Future Opportunities. Biomedicines. 2026 Jan 19;14(1):213. doi: 10.3390/biomedicines14010213.

  PMID: 41595747 BACKGROUND

• Vakili S, Koohpeyma F, Samare-Najaf M, Namavar Jahromi B, Jafarinia M, Goharitaban S, Savardashtaki A, Samareh A, Amini F, Hashempur MH. Investigating the effects of rosmarinic acid on ovarian tissue, inflammatory markers, and sex hormones in polycystic ovary syndrome rats. Physiol Rep. 2025 Apr;13(7):e70304. doi: 10.14814/phy2.70304.

  PMID: 40170546 BACKGROUND

• Chen T, Jia F, Yu Y, Zhang W, Wang C, Zhu S, Zhang N, Liu X. Potential Role of Quercetin in Polycystic Ovary Syndrome and Its Complications: A Review. Molecules. 2022 Jul 13;27(14):4476. doi: 10.3390/molecules27144476.

  PMID: 35889348 BACKGROUND

• Lonardo MS, Cacciapuoti N, Guida B, Di Lorenzo M, Chiurazzi M, Damiano S, Menale C. Hypothalamic-Ovarian axis and Adiposity Relationship in Polycystic Ovary Syndrome: Physiopathology and Therapeutic Options for the Management of Metabolic and Inflammatory Aspects. Curr Obes Rep. 2024 Mar;13(1):51-70. doi: 10.1007/s13679-023-00531-2. Epub 2024 Jan 3.

  PMID: 38172476 BACKGROUND

• Manouchehri A, Abbaszadeh S, Ahmadi M, Nejad FK, Bahmani M, Dastyar N. Polycystic ovaries and herbal remedies: A systematic review. JBRA Assist Reprod. 2023 Mar 30;27(1):85-91. doi: 10.5935/1518-0557.20220024.

  PMID: 35916457 BACKGROUND

• Ndefo UA, Eaton A, Green MR. Polycystic ovary syndrome: a review of treatment options with a focus on pharmacological approaches. P T. 2013 Jun;38(6):336-55.

  PMID: 23946629 BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility; Metabolic Diseases; Insulin Resistance

Interventions

Metformin

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; Nutritional and Metabolic Diseases; Hyperinsulinism; Glucose Metabolism Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Dr. Anosh Tahir, PhD Scholar

CONTACT

+923362189125; dr.anoshtahir@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The study record explicitly states it is open-label, meaning no participants, care providers, investigators, or outcome assessors are blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: May 22, 2026
• Study Start: April 10, 2025
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): June 15, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)