Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Polycystic Ovary Syndrome (PCOS)

Treatments: Drug: Placebo; Drug: Dihydroartemisinin

Study type: Interventional

Funder types: Other

Identifiers

NCT06842524

B2024-417(2)

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: Female

Ages: 18 to 40 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 2 patient groups, including a placebo group

Dihydroartemisinin Arm

Active Comparator group

Description:

Dihydroartemisinin tablets 40mg tid for 90 days

Treatment:

Drug: Dihydroartemisinin

Placebo Arm

Placebo Comparator group

Description:

Idential placebo tid for 90 days

Treatment:

Drug: Placebo