RECRUITINGPhase 2INTERVENTIONAL

Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome

Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome: a Multi-centre Placebo-controlled Randomized Clinical Trial

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - Patients on oral contraceptives. A two-month waiting period after previous treatment 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. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

DRUG

Dihydroartemisinin

Dihydroartemisinin tablets 40mg tid po for 90 days

DRUG

Placebo

Identical placebo tid for 90 days

Locations (4)

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

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

Xiamen, Fujian, China

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China