Clinical trial NCT06842524: Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome
Official title: Dihydroartemisinin for the Treatment of Polycystic Ovary Syndrome: a Multi-centre Placebo-controlled Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Polycystic Ovary Syndrome (PCOS)
Keywords: Polycystic Ovary Syndrome
Dihydroartemisinin
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2025-02-24
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The occurrence of a regular menstrual cycle
timeFrame: From the start of treatment to the end of follow-up at 26 weeks
Secondary outcomes:
measure: The presence of a dominant follicle
timeFrame: From the start of treatment to the end of follow-up at 26 weeks
measure: The number of bilateral antral follicles
timeFrame: Before and immediately after 90-day treatment
measure: Serum AMH
timeFrame: Before and immediately after 90-day treatment
measure: Serum total testosterone
timeFrame: Before and immediately after 90-day treatment
measure: Serum sex hormone binding globulin (SHBG)
timeFrame: Before and immediately after 90-day treatment
measure: free androgen index (FAI)
timeFrame: Before and immediately after 90-day treatment
measure: HOMA-IR
timeFrame: Before and immediately after 90-day treatment
Other outcomes:
Locations:
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Xiamen
country: China
facility: Women and Children's Hospital, School of Medicine, Xiamen University
state: Fujian
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Reproductive Medicine Center, Zhongshan Hospital, Fudan University
name: Xi Dong, MD
role: STUDY_CHAIR
affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
name: Xiaoying Li, MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University
name: Jingjing Jiang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Obstetrics and Gynaecology, Monash University
name: Ben Willem Mol, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Perinatal Epidemiology and Statistics Unit, Centre for Big Data Research in Health, University of New South Wales
name: Wentao Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: