The effect of acupuncture or metformin for improvement of insulin sensitivity in women with Polycystic Ovary Syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska Institutet

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Hormonal diseases [C19], Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]

Trial duration

18 Oct 2024 → ongoing

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514505-64-01

EudraCT number

2015-004250-18

ClinicalTrials.gov

NCT02647827

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Primary objective
• To determine the clinical effectiveness of 4 months of 1) acupuncture + lifestyle management and 2) metformin + lifestyle management compared with 3) lifestyle management only for improvement of insulin sensitivity as measured by HOMA-IR, by the insulin response to glucose assessed by calculating the area under the curve (AUCinsulin) during the oral glucose tolerance test (OGTT), and by glucose regulation (assessed by analyzing Hba1c levels).

Secondary objectives 1

1. Secondary objectives • To evaluate changes in secondary metabolic measures, including fasting insulin, c-peptide, glucose, and adipokines, calculation of HOMA-B (i.e. the Islet β-cell function) and the c-peptide index, assessment of the adipokines and lipid profile, body size and proportions and body fat distribution. • To determine changes in gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle and endometrial tissue biopsies, and biomarkers in whole blood. • To evaluate endocrine measures including menstrual pattern and ovulation frequency, circulating hormones (sex steroids, AMH, gonadotropins), and excretion of metabolites of sex steroids in urine. • To determine changes in women’s health related quality of life (HRQL) and symptoms of anxiety and depression, and negative side-effects. • To evaluate the cost-effectiveness of the different treatments.

Conditions and MedDRA coding

Polycystic ovary syndrome

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Inclusion criteria – women with PCOS 1. Age 18 to 40 years 2. BMI ≥25 to ≤45 (≥23 to ≤37.5 Chinese) given that 95% of all women with PCOS with a BMI 25 are insulin resistant (27, 28). 3. PCOS diagnosis according to Rotterdam criteria 2003 with at least two of the following three symptoms (29): Clinical signs of hyperandrogenism (hirsutism or acne); oligo/amenorrhea; and/or polycystic ovaries (PCOS). Hirsutism is defined as a self-reported Ferriman-Gallwey (FG) score ≥8 (≥5 Chinese) (30, 31). Acne is defined by a positive response to the question Do you have acne? Oligomenorrhea is defined as an intermenstrual interval >35 days and <8 menstrual bleedings in the past year. Amenorrhea as <3 cycles per year. PCO is defined by transvaginal ultrasound with ≥12 follicles 2–9 mm and/or ovarian volume ≥10 ml in one or both ovaries. 4. Willing to sign the consent form. Inclusion criteria – controls Controls should have BMI >25 to <45, regular cycles with 28 days ± 2 days, no signs of hyperandrogenism. They are excluded if they have menstrual irregularities, signs of hyperandrogenism (FG >4), evidence of PCO morphology on ultrasound.

Exclusion criteria 1

1. Exclusion criteria for all women 1. Age >40 2. Exclusion of other endocrine disorders such as non-classic congenital adrenal hyperplasia (17-hydroxyprogesterone < 3nmol/L), androgen secreting tumors or suspected Cushing’s syndrome. 3. Having known kidney disease, autoimmune disorders or cancer. 4. Type I diabetes. 5. Pharmacological treatment (cortizon, antidepressant, other antidiabetic treatment such as insulin and acarbose, hormonal contraceptives, hormonal ovulation induction or other drugs judged by discretion of investigator) within 12 weeks. Depo Provera or similar within 6 months. 6. Blood pressure >160 / 100 mmHg 7. Pregnancy or breastfeeding the last 6 months 8. Acupuncture last 2 months 9. Daily smoking and alcoholic intake 10. Language barrier or disabled person with reduced ability to understand information.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Changes in insulin sensitivity after 16 weeks of intervention as measured by HOMA-IR, by the insulin response to glucose assessed by calculating the area under the curve (AUCinsulin) during the oral glucose tolerance test (OGTT), and by glucose regulation (assessed by analyzing Hba1c levels).

Secondary endpoints 1

1. After 4 months of intervention: • Changes in secondary metabolic measures, including fasting insulin, c-peptide, glucose, and adipokines, calculation of HOMA-B (i.e. the Islet β-cell function) and the c-peptide index, assessment of the adipokines and lipid profile, body size and proportions and body fat distribution. • Changes in gene expression and DNA methylation profiles related to insulin sensitivity in fat, muscle and endometrial tissue biopsies, and biomarkers in whole blood. • Changes in

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska Institutet

Sponsor organisation

Karolinska Institutet

Address

Nobels Vag 6

City

Solna

Postcode

171 65

Country

Sweden

Scientific contact point

Organisation

Karolinska Institutet

Contact name

Elisabet Stener-Victorin

Public contact point

Organisation

Karolinska Institutet

Contact name

Elisabet Stener-Victorin

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications