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Polycystic Ovarian Syndrome (PCOS)Phase 1NAE-PCOSNCT07603505

Effect of NAE on Polycystic Ovarian Syndrome (PCOS)

A Phase 1 study testing Herbal Formulation, Metformin XR and Metformin 750 mg and herbal formulation 500 mg in people with Polycystic Ovarian Syndrome (PCOS) and Infertility, run by Jinnah Sindh Medical University at 1 site in Pakistan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 40 years, women only
What is being tested?
Herbal Formulation, Metformin XR and Metformin 750 mg and herbal formulation 500 mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
116 participants
Where
1 sitePakistan
Study dates
10 Apr 2025to 15 Jun 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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).

Trial locations and contacts

1 site in 1 country.

Pakistan1 site

  • Jinnah Postgraduate Medical Centre

    Karachi, Sindh

Other trials in Pakistan

About this study

Official title: Effect of Nepeta Adenophyta Hedge Extract and Its Fractions on Polycystic Ovarian Syndrome (PCOS)

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.

Read the detailed description

Polycystic Ovarian Syndrome indicates an increasing health challenge for women of reproductive age, with global prevalence estimates between 6% and 14%. Individuals affected often experience psychological distress, metabolic issues, and difficulties with fertility. The pathophysiology of PCOS consists of three interrelated axes: (i) heightened GnRH pulse frequency results in an increased LH/FSH ratio and theca cell hyperplasia, driving ovarian hyperandrogenism; (ii) peripheral insulin resistance coupled with compensatory hyperinsulinemia further enhances ovarian androgen production; and (iii) chronic oxidative stress and inflammation, driven by cytokines from adipose tissue (TNF α, IL 6) and reactive oxygen species, which hinder follicular development and exacerbate metabolic dysfunction.

Traditional first-line therapies - metformin (insulin sensitizer), clomiphene citrate (ovulation stimulant), and spironolactone (anti-androgen) - each address only a single facet of the syndrome and have notable drawbacks: metformin can lead to dose-dependent gastrointestinal issues; clomiphene elevates the risk of multiple pregnancies and presents anti-estrogenic side effects; spironolactone is teratogenic and is unsuitable for women attempting to conceive. Additionally, none of these agents concurrently tackle hyperandrogenism, insulin resistance, inflammation, and oxidative stress.

Herbal remedies provide a multifaceted, multi-target strategy that corresponds effectively with the intricate pathophysiology of PCOS. NAE shows considerable potential. Its flavonoid fraction (luteolin, apigenin, quercetin) acts as a free radical scavenger, inhibits lipid peroxidation, enhances endogenous antioxidant enzymes (superoxide dismutase, glutathione peroxidase), and down regulates 17α hydroxylase, thereby reducing ovarian testosterone production. The phenolic acids (caffeic acid, rosmarinic acid) inhibit pro-inflammatory cytokines TNF α and IL 6, while improving insulin sensitivity through the enhancement of GLUT 4 translocation in adipose tissue and skeletal muscle. Terpenoids (nepetalactones) influence the hypothalamic pituitary gonadal axis, aiding in the normalization of the LH/FSH ratio, while also offering anxiolytic effects that might alleviate stress-related hormonal disturbances. Glycosides and reducing sugars enhance insulin receptor signaling, stimulate hepatic glycogen production, and block gluconeogenic enzymes like glucose 6 phosphatase.

These mechanistic predictions were confirmed in a carefully regulated animal study. PCOS was established in female Albino Wistar rats through Letrozole (1 mg/kg) given orally dissolved in 0.5% carboxymethylcellulose (CMC) for 21 days. The animals were split into 07 categories, which included untreated control, PCOS control, metformin standard (350 mg/kg), crude NAE (low dose 350 mg/kg, high dose 500 mg/kg), methanol fraction (64 mg/kg), and butanol fraction (12.5 mg/kg), given orally for 30 days. Essential discoveries comprised:

  • Hormonal: Significant reduction in serum LH and total testosterone, with normalisation of the LH/FSH ratio (p < 0.01).
  • Metabolic: Decreased fasting blood sugar, reduced HOMA IR, enhanced lipid profile (lowered total cholesterol, triglycerides, LDL; raised HDL).
  • Ovarian structure: Normal follicular arrangement on H\&E staining.
  • Gene expression: qRT PCR of ovarian tissue showed an increase in the anti-inflammatory cytokine IL-4, whereas androgen receptor (AR), toll-like receptor 4 (TLR4), Cytochrome-17 (CYP-17), tumor necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) were significantly decreased.

No mortality or signs of hepatorenal toxicity were observed at any dose. Considering this strong preclinical evidence, the current clinical trial aims to apply these results to human PCOS patients. The research will recruit 116 women diagnosed with PCOS according to Rotterdam criteria and having insulin resistance (HOMA IR > 2.00). Participants will be assigned randomly to three parallel groups: (1) NAE extract 500 mg two times a day; (2) metformin XR 750 mg two times a day; (3) a combination of both. The duration of the treatment is 4 months. The main goal is the reestablishment of normal ovulatory menstrual cycles (21-35 days) verified by ultrasound. Secondary outcomes consist of alterations in serum LH, FSH, testosterone, HOMA IR, HbA1c, Fasting Insulin, Body weight, and quality of life specific to PCOS (PCOSQOL). Safety will be assessed via the recording of adverse events, tests for liver and kidney function, and a comprehensive blood count.

Being tested
Herbal Formulation, Metformin XR, Metformin 750 mg and herbal formulation 500 mg
Keywords
Polycystic Ovarian Syndrome (PCOS), NAE extract, metabolic disorder, herbal medicine, insulin resistance, metformin
Medical subject headings
Polycystic Ovary Syndrome, Infertility, Metabolic Diseases, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Herbal FormulationDrug

    NAE 500 mg twice daily for 4 months in PCOS patients

  • Metformin XRDrug

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

  • Metformin 750 mg and herbal formulation 500 mgDrug

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

Study groups in NCT07603505
Study groupRoleWhat they receive
NAE treated groupExperimentalNAE 500 mg twice daily for 4 months in PCOS patients
Receives: Drug: Herbal Formulation
Metformin XR treated groupActive comparatorMetformin XR 750 mg twice daily for 4 months in PCOS patients
Receives: Drug: Metformin XR
Adjunct GroupExperimentalNAE 500 mg and Metformin XR 750 mg twice daily for 4 months in PCOS patients
Receives: Drug: Metformin 750 mg and herbal formulation 500 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Achieving Menstrual Cycle Normalization After 4 Months of Treatment

    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.

    Measured: Baseline to 4 months

Secondary outcomes (7)

  1. Body Weight Changes

    Change in body weight measured using a calibrated weighing scale. Unit: kg

    Measured: Baseline and 4 months

  2. Serum Follicle-Stimulating Hormone (FSH) Levels

    Change in serum FSH levels assessed by standard laboratory assays, reported in mIU/mL. Reference ranges: Follicular phase 3.5-12.5, Ovulatory phase 4.7-21.5, Luteal phase 1.7-7.7

    Measured: Baseline and 4 months

  3. Serum Luteinizing Hormone (LH) Levels

    Change in serum LH levels assessed using standard laboratory assays, expressed in mIU/mL. Reference ranges are 1.9-9.2 during the follicular phase, 6.1-49.1 during ovulation, and 1.3-10.8 in the luteal phase

    Measured: Baseline and 4 months

  4. Serum Testosterone Levels

    Change in serum testosterone levels determined using standard laboratory assays, expressed in ng/mL. Normal reference range for individuals aged 18-49 years is 0.084-0.481 ng/mL.

    Measured: Baseline and 4 months

  5. Glycated Hemoglobin (HbA1c) Level

    Change in HbA1c (%) measured using standardized laboratory methods. Reference ranges: Normal <5.6%, Prediabetes 5.7-6.4%, Diabetes ≥6.5%

    Measured: Baseline and 4 months

  6. Fasting Serum Insulin Concentration

    Change in fasting serum insulin levels assessed using standard laboratory assays, expressed in µIU/mL. Normal reference range: 2-25 µIU/mL.

    Measured: Baseline and 4 months

  7. HOMA-IR

    HOMA-IR will be calculated at baseline and after 4 months using the formula: HOMA-IR = [fasting plasma glucose (mmol/L) × fasting insulin (μU/mL)] ÷ 22.5

    Measured: Baseline and 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2026
  2. Study start10 Apr 2025
  3. Primary completion30 May 2026
  4. Study completion15 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
116 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07603505
Sponsor's protocol ID
NAE-PCOS-2024
Other IDs
NO.F.2-81/2024-GENL/101/JPMC
Acronym
NAE-PCOS
Status last verified
May 2026
First submitted
18 May 2026
Last updated
22 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual participant data will not be shared due to privacy and confidentiality concerns of study participants, and because the study is not funded by external agencies requiring data sharing.

Publications

  • 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.

    PubMed 41593809

  • 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.

    PubMed 40013621

  • 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.

    PubMed 37762427

  • 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.

    PubMed 41487516

  • 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.

    PubMed 41761211

  • 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.

    PubMed 27777110

  • 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.

    PubMed 33307050

  • 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.

    PubMed 41595747

  • 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.

    PubMed 40170546

  • 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.

    PubMed 35889348

  • 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.

    PubMed 38172476

  • 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.

    PubMed 35916457

  • 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.

    PubMed 23946629

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Herbal Formulation, Metformin XR and Metformin 750 mg and herbal formulation 500 mg in people with Polycystic Ovarian Syndrome (PCOS) and Infertility, run by Jinnah Sindh Medical University at 1 site in Pakistan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Achieving Menstrual Cycle Normalization After 4 Months of Treatment (time frame: Baseline to 4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07603505, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.

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