Clinical Observation on Kuntai Capsule in Treating Early-onset Ovarian Hypofunction

A Multi-center Clinical Study on the Efficacy and Safety of Kuntai Capsule Alone and in Combination With Hormones in the Treatment of Early-onset Hypoovarian Function

To evaluate the efficacy and safety of Kuntai capsule alone or combined with hormone therapy in improving ovarian function in POI patients (including subclinical stage).

Study Overview

• Status: Recruiting
• Conditions: Primary Ovarian Insufficiency
• Intervention / Treatment: Drug: Kuntai Capsule; Drug: Femoston

Detailed Description

The study is expected to be conducted between 2021.08 and 2023.12.120 subjects with early-onset ovarian insufficiency will be randomly assigned to trial, control, or combination groups using a computer-generated randomization table.By comparing the data of primary efficacy indexes, secondary efficacy indexes and safety indexes before and after medication, The principal investigator will write and publish the paper.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yuquan Zhang, Professor; Phone Number: +8613706299363; Email: jsnt_zhangyuquan@163.com
• Study Contact Backup: Name: Weina Wang, Postgraduate; Phone Number: 13795242689; Email: 451579895@qq.com

Study Locations

• China
  • Jiangsu
    • Hai'an, Jiangsu, China, 226600
      • Recruiting
      • Hai'an People's Hospital
      • Contact: Hong Lu, master; Phone Number: 13862711105
    • Huai'an, Jiangsu, China, 226600
      • Recruiting
      • Hai'an Hospital of traditional Chinese Medicine
      • Contact: Ling Chen, master; Phone Number: 18934506298
    • Nantong, Jiangsu, China
      • Recruiting
      • Affiliated Hospital of Nantong University
      • Contact: Yuanquan Zhang, Professor; Phone Number: +8613706299363; Email: jsnt_zhangyuquan@163.com
    • Nantong, Jiangsu, China, 226001
      • Recruiting
      • Nantong First People's Hospital
      • Contact: Yanli Zheng, Master; Phone Number: +8613962910099
    • Nantong, Jiangsu, China, 226001
      • Recruiting
      • Nantong Hospital of Traditional Chinese Medicine
      • Contact: Dongmei C Chen, Master; Phone Number: 13485105619
    • Ru'gao, Jiangsu, China, 226500
      • Recruiting
      • Rugao Boai Hospital
      • Contact: Sifang Zhang, bachelor; Phone Number: 18752861616

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. The women aged <40 years old.
2. Serum basal follicle stimulating hormone (FSH) level ≥15 IU/L at least twice inspection (two occasions >4 weeks apart). Rare menstruation or menopause for at least 4 months.
3. Individuals meeting the above criteria who voluntarily consented to study participation.

Exclusion Criteria:

1. Pregnant and lactating patients;
2. Patients with endometriosis, adenomyosis, endometrial lesions (submucous fibroids, endometrial polyps, etc.), hysteromyoma > 4cm or hysterectomy;
3. Patients with known or suspected breast cancer history and estrogen-dependent malignant tumor;
4. Patients with personal history of venous thromboembolism (VTE) or high risk of VTE (including body mass index > 30 kg/m2, smoking and family history of thrombosis);
5. Patients with porphyria;
6. Patients with serious primary diseases or mental illness such as cardiovascular, liver, kidney and hematopoietic system;
7. Patients who are participating in other clinical trials or have participated in other clinical trials in the past three months;
8. Patients who suspect or have a history of alcohol and drug abuse;
9. Patients who are known to be allergic to the test drugs or their components;
10. The researchers determined that patients are not suitable for this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: FACTORIAL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: POI patients who taking Kuntai capsule; Patients in this group will take Kuntai capsule orally, 4 capsules each time, 3 times a day, and take the medicine for 3 courses.	Drug: Kuntai Capsule; The instructions is pointed that each Kuntai capsule is 0.5g and the usage of Kuntai capsule is oral taking 4 capsules each time, 3 times a day, and 4 weeks is a course of treatment. The patients will taking 3 courses of treatment in this study.; Other Names: Kuntai Jiaonang
ACTIVE_COMPARATOR: POI patients who accepting hormone therapy; The estrogen and progesterone sequential regimen was adopted. The drug was estradiol tablets/estradiol didroxyprogesterone tablets (Femoston). Red tablets (estradiol, 2mg/d) were taken in the first 14 days, and gray tablets (estradiol, 2mg/d, dydrogesterone,10 mg/d) were taken in the last 14 days. 28 days was a course of treatment, and 3 courses of treatment were taken.	Drug: Femoston; The estrogen and progesterone sequential regimen was adopted. The Femoston was contain estradiol tablets and estradiol didroxyprogesterone tablets. Red tablets (estradiol, 2 mg/d) were taken in the first 14 days, and gray tablets (estradiol, 2 mg/d, dydrogesterone,10 mg/d) were taken in the last 14 days. 28 days was a course of treatment, and three courses of treatment were taken. The patients will taking 3 courses of treatment in this study.; Other Names: Complex Packing Estradiol Tablets/Estradiol and Dydrogesterone Tablets
EXPERIMENTAL: POI patients who taking Kuntai capsule combined with hormone therapy; Kuntai capsule was taken at the same dose as Kuntai group on the basis of hormone therapy for 3 courses.	Drug: Kuntai Capsule; The instructions is pointed that each Kuntai capsule is 0.5g and the usage of Kuntai capsule is oral taking 4 capsules each time, 3 times a day, and 4 weeks is a course of treatment. The patients will taking 3 courses of treatment in this study.; Other Names: Kuntai Jiaonang; Drug: Femoston; The estrogen and progesterone sequential regimen was adopted. The Femoston was contain estradiol tablets and estradiol didroxyprogesterone tablets. Red tablets (estradiol, 2 mg/d) were taken in the first 14 days, and gray tablets (estradiol, 2 mg/d, dydrogesterone,10 mg/d) were taken in the last 14 days. 28 days was a course of treatment, and three courses of treatment were taken. The patients will taking 3 courses of treatment in this study.; Other Names: Complex Packing Estradiol Tablets/Estradiol and Dydrogesterone Tablets
EXPERIMENTAL: Subclinical POI patients who taking Kuntai capsule; Subclinical POI patients in this group which with Kuntai capsule intervention. This group is a self-controlled experiment before and after treatment	Drug: Kuntai Capsule; The instructions is pointed that each Kuntai capsule is 0.5g and the usage of Kuntai capsule is oral taking 4 capsules each time, 3 times a day, and 4 weeks is a course of treatment. The patients will taking 3 courses of treatment in this study.; Other Names: Kuntai Jiaonang

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follicle-stimulating hormone (FSH)	Changes of the level of FSH before and after treatment	Baseline, 3 months, 6 months
Kupperman Score	Changes of the Kupperman score before and after treatment，Kupperman Score ranges from 0 to 69, with the smaller the score, the better off the subject	Baseline, 3 months, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Luteinizing hormone (LH)	Changes of the level of LH before and after treatment	Baseline, 3 months, 6 months
Estradiol hormone (E2)	Changes of the level of Estradiol hormone before and after treatment	Baseline, 3 months, 6 months
Antral follicle count (AFC)	Changes of the AFC before and after treatment	Baseline, 3 months,
anti-Müllerian hormone (AMH)	Changes of the level of AMH before and after treatment	Baseline, 3 months,
The peak systolic blood flow velocity （PSV）	The peak systolic blood flow velocity before and after treatment was assessed by vaginal B ultrasound	Baseline, 3 months,
The end-diastolic blood flow velocity（EDV）	The uterine artery end-diastolic blood flow velocity before and after treatment was assessed by vaginal B ultrasound	Baseline, 3 months,
Uterine artery resistance index（RI）	The uterine artery resistance index before and after treatment was assessed by vaginal B ultrasound	Baseline, 3 months,
Proportion of patients with normal menstruation	To measure the ratio of patients have normal menstruation after treatment	Baseline，3 months, 6 months, 9 months
Pregnancy situation	To ask the patient if there is pregnancy (for patient who has pregnancy need)	6 months

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Nantong University
• Investigators: Principal Investigator: Yuquan Zhang, Professor, Affiliated Hospital of Nantong University

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 22, 2021
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: August 4, 2021
• First Submitted That Met QC Criteria: August 19, 2021
• First Posted (ACTUAL): August 25, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2022
• Last Update Submitted That Met QC Criteria: September 8, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Primary Ovarian Insufficiency; Menopause, Premature; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins; Estradiol; Dydrogesterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate
• Other Study ID Numbers: AHNantong-POI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not planning sharing at present.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No