The Effect of Dihydroartemisinin in PCOS

The Evaluation of the Effect of Dihydroartemisinin in Patients With Polycystic Ovary Syndrome

Artemisinin has been widely used as a first-line antimalarial drug in routine clinical practice. In recent years, it has been reported that Artemisinin also has some significant anti-inflammatory, anti-tumor and immune-modulating effects. The investigators' previous studies discovered that Artemisinin dramatically reduced serum androgen levels and improved poly-cystic ovary syndrome(PCOS) in animals. Preliminary study by the investigators found that artemisinin derivatives are capable of reducing both androgen levels and improving insulin resistance, two clinical characteristics of PCOS. Thus artemisinin derivatives has the potential effect to alleviate PCOS symptoms. The current study aims to investigate the effect of artemisinin on improving PCOS and serum androgen levels in PCOS subjects.

Study Overview

• Status: Recruiting
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Dihydroartemisinin

Detailed Description

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine metabolic disorder caused by a combination of genetic and environmental factors. The pathogenesis of PCOS remains unclear. Artemisinin has been widely used as a first-line antimalarial drug in routine clinical practice. In recent years, it has been reported that Artemisinin has significant anti-inflammatory, anti-tumor and immune-modulating effects. The investigator's previous studies found that artemisinin and its derivatives could significantly promote uncoupling protein 1 (UCP1) transcription and the conversion of white fat to brown fat. Artemisinin derivatives upregulated the levels of genes critical for brown fat differentiation and function, accompanied by enhanced mitochondrial biosynthesis, demonstrating their potential to promote white fat browning and improve metabolism in rodent models. The investigators also observed that androgen levels in drug-induced PCOS rats were reduced, when treated with artemether analogs for prophylactic and therapeutic purposes, respectively. It is believed that the two core mechanisms in the pathogenesis of PCOS are excessive androgen synthesis and insulin resistance. Preliminary study by the investigators found that artemisinin derivatives are capable of reducing both serum androgen levels and improving insulin resistance, two clinical characteristics of PCOS. Thus artemisinin derivatives has the potential effect to alleviate PCOS symptoms and control or even reverse the disease progression. The current study aims to investigate the effect of artemisinin on improving PCOS and serum androgen levels in PCOS subjects.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: JINGJING JIANG, MD; Phone Number: 692023 +862164041990; Email: jiang.jingjing@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Zhongshan Hospital Fudan University
    • Contact: JINGJING JIANG, MD; Phone Number: 692023 +862164041990; Email: jiang.jingjing@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI 23-30kg/M2
• No plan for pregnancy in the coming 6 months
• Newly diagnosed PCOS, or PCOS without any medication for the past three months.

• Patients should meet all the three following criteria:

  1. Oligomenorrhea or amenorrhea: Oligomenorrhea is defined as more than 35 days between menstrual periods and less than 8 menstrual bleedings in the past year; amenorrhea is defined as more than 90 days between two menstrual bleedings.
  2. Polycystic ovaries: ≥12 follicles in both ovaries (diameter<10mm), confirmed by ultrasound.
  3. Elevated androgen levels: testosterone>1.67 nmol/L.

Exclusion Criteria:

• Previously treated with steroids or other medications for PCOS in the past 3 months.
• Patients with other endocrine diseases that can cause secondary PCOS, including but not limited to: 21 hydroxylase deficiency, prolactinoma, hypothyroidism, Cushing's syndrome, etc.
• Pregnancy.
• Patients with other serious diseases affecting heart, liver, kidney, or other major organs.
• Patients with any type of cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dihydroartemisinin Group; The subjects take Dihydroartemisinin, 40mg tid for 12 weeks	Drug: Dihydroartemisinin; Dihydroartemisinin 40mg three times a day for 12 consecutive weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of regular menses by questionnaire	Periodical vaginal bleeding by questionnaire	12 weeks
Bilateral ovary volume	Length, width and height of bilateral ovaries measured by B type ultrasound	12 weeks
Number of immature follicles	Total number of follicles with diameters <10 mm measured by B type ultrasound	12 weeks
Serum testosterone levels	Measurement of serum total testosterone	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum anti-Mullerian hormone	Measurement of serum AMH	12 weeks
Sex hormone binding globulin (SHBG)	Measurement of serum SHBG	12 weeks
Serum dehydroepiandrosterone sulfate	Measurement of serum DHEA	12 weeks after drug intervention

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Xiaoying Li, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): June 30, 2023
• Study Completion (Estimated): August 31, 2023

Study Registration Dates

• First Submitted: July 10, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Polycystic Ovary Syndrome; Syndrome; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Artenimol
• Other Study ID Numbers: B2020-115R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No