Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome

Phase 2RecruitingNCT06842524

Shanghai Zhongshan Hospital150 enrolled

Overview

Polycystic ovarian syndrome (PCOS) is the most frequent endocrine disorder affecting women of reproductive age, with a prevalence of 10 to 13%. PCOS is characterized by irregular menstrual cylcles/ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. For infertile patients seeking ovulation induction, letrozole is the drug of first choice. For PCOS patients not seeking pregnancy, there exists a variety of treatments to alleviate symptoms. It has been demonstrated that artemisinin derivatives can promote energy expenditures and insulin sensitivity by activating thermogenic adipocytes, thereby protecting against diet-induced obesity and metabolic disorders in rodents. Recently, we showed in a single arm pilot study including 19 PCOS-patients, that dihydroartemisinin ameliorated hyperandrogenemia reduced antral follicle count and normalized menstrual cycles. Based on these findings, we aim to evaluate the efficacy of dihydroartemisinin in women with PCOS in a placebo controlled randomized clinical trial. The primary outcome is return of regular menstrual cycles within 6 months after start of treatment, with antral follicle count and metabolic profile being secondary outcomes. The results will potentially impact the standard of care for patients diagnosed with PCOS.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

150

Conditions

Polycystic Ovary Syndrome (PCOS)

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Women with PCOS defined as having irregular menstrual cycles and hyperandrogenism. Irregular menstrual cycles are defined as \< 21 or \> 35 days or \< 8 cycles per year. Hyperandrogenism refers to either hyperandrogenemia or hirsutism. Hyperandrogenemia will be defined as an elevated total testosterone \>1.67 nmol/L measured by Elecsys Testosterone II (Roche Diagnostics). Hirsutism is determined by a modified Ferriman-Gallwey Score \>4 at screening exam. * Body Mass Index (BMI) between 18.5 and 28 kg/M2 * Negative pregnancy test * No plan for pregnancy in the coming 6 months Exclusion Criteria: * Patients on oral contraceptives. A two-month washout period will be required prior to screening for patients on these agents. A one-month washout will be required for patients on oral cyclic progestins. Patients on depo-progestins or hormonal implants are excluded. * Patients with liver disease defined as ALT or AST above normal range of each participating center, or total bilirubin\>30umol/L. Metabolic dysfunction-associated steatotic liver disease (MASLD) with normal ALT and AST can be included. * Patients with anemia (Hemoglobin \< 12 g/dL) or neutropenia (neutrocyte \<1.8×10\^9/L). * Patients with renal disease defined as serum creatinine\> 115umol/L. * Patients diagnosed with other endocrine diseases that are known to cause secondary polycystic ovary morphology, e.g., Cushing's syndrome, hyperprolactinemia, congenital adrenal hyperplasia (21-hydroxylase deficiency or other enzyme deficiency), hypothyroidism, etc. * Patients diagnosed with Type 1 or Type 2 diabetes. * Patients with known heart disease, like heart failure, atrial fibrillation, coronary heart disease, etc. * Patients with a history of any type of cancer. * Patients taking other medications known to affect reproductive function or metabolism. These medications include GnRH agonists and antagonists, antiandrogens, gonadotropins, GLP-1 receptor agonist, SGLT2i, metformin and thiazolidinediones. The washout period on all these medications will be two months. * Patients who have undergone a bariatric surgery procedure within the past 12 months.

Locations (4)

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

RECRUITING

Women and Children's Hospital, School of Medicine, Xiamen University

Xiamen, Fujian, China

RECRUITING

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

RECRUITING

Outcomes

Primary Outcomes

The occurrence of a regular menstrual cycle

The occurrence of a regular menstrual cycle is defined as at least three consecutive spontaneous vaginal bleedings lasting for 2-7 days, with intervals between the start of each cycle of 21 and 35 days (inclusive), during the 26-week period after initiating treatment.

Time frame: From the start of treatment to the end of follow-up at 26 weeks

Secondary Outcomes

The presence of a dominant follicle

This will be verified by transvaginal/transanal ultrasound before predicted ovulation, or testing serum progesterone in the predicted mid-luteal phase (A progesterone level\>16nmol/L or 5ng/ml is suggestive of ovulation) in those with at least two consecutive spontaneous bleedings.

Time frame: From the start of treatment to the end of follow-up at 26 weeks

The number of bilateral antral follicles

This will be measured by transvaginal/transanal ultrasound before and immediately after 90-day treatment. Antral follicles are defined as follicles measuring 2-9 mm in diameter in the ovary.