Using Preimplantation Genetic Diagnosis in Autosomal Dominant Polycystic Kidney Disease Patients: a Multicenter Clinical Trial (ESPERANCE)

Efficacy and Safety of Preimplantation Genetic Diagnosis in Blocking Pathogenic Gene Inheritance for Autosomal Dominant Polycystic Kidney Disease: a Multicenter Clinical Trial

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease in humans. ADPKD may affect all the generations of the ADPKD family and the probability of ADPKD is 50% in the second generation for each gender. It has been confirmed that PKD1 and PKD2 are two pathogenic genes of ADPKD. Nowadays, the investigators have established an effective gene detection technology platform for PKD1/2 gene with long fragment PCR and next generation sequencing. First, the investigators performed genetic testing in patients with clinically diagnosed ADPKD and strong fertility desire, but afraid of hereditary risk. Using Preimplantation genetic diagnosis, including multiple annealing and looping-based amplification cycles amplification technique, the investigators successfully screened out healthy embryos by In Vitro Fertilization. Then the investigators transplanted embryos returned to the parent. When the baby is born, using umbilical cord blood gene detection, the investigators confirmed that the neonates do not inherit genetic defects form parents. The investigators have succeeded in one couple. The investigators design a multicenter clinical trial to confirm those procedures efficacy and safety.

Study Overview

• Status: Completed
• Conditions: Polycystic Kidney, Type 1 Autosomal Dominant Disease
• Intervention / Treatment: Procedure: Preimplantation Genetic Diagnosis

• Study Type: Interventional
• Enrollment (Actual): 459
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • The First affiliated Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100000
      • Navy General Hospital
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Southwest Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Fuzhou General Hospital
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Sun Yat-sen University
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China, 050000
      • Hebei Province Center for Reproductive Medicine
    • Shijiazhuang, Hebei, China, 050000
      • The Third Hospital of Hebei Medical University
  • Henan
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Renmin Hospital of Wuhan University
    • Wuhan, Hubei, China, 430000
      • Wuhan Tongji Hospital
    • Wuhan, Hubei, China, 430000
      • Wuhan Union Hospital
  • Hunan
    • Changsha, Hunan, China, 410000
      • Reproductive & Genetic Hospital of Citic-Xiangya
    • Changsha, Hunan, China, 410000
      • Second Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410000
      • Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
    • Nanjing, Jiangsu, China, 210000
      • The First Affiliated Hospital with Nanjing Medical University
    • Suzhou, Jiangsu, China, 215000
      • The First Affiliated Hospital of Soochow University
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Shengjing Hospital
  • Shandong
    • Jinan, Shandong, China, 250000
      • Hospital for Reproductive Medicine Affiliated to Shandong University
    • Jinan, Shandong, China, 250000
      • Shandong Provincial Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Shanghai Changzheng Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Provincial People's Hospital
    • Xi'an, Shanxi, China, 710000
      • Tang-Du Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Hospital of Sichuan University
    • Chengdu, Sichuan, China, 610000
      • Shanxi Provincial People's Hospital
    • Chengdu, Sichuan, China, 610000
      • West China Second University Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Sir Run Run Shaw Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Only one ADPKD patient in one couple without gender limitation
• Wife has age limitation from 20 years to 35 years
• ADPKD ADPKD diagnosis with or without family history
• Find out specific pathogenic mutations in the PKD1 gene with at least one of the following: one of family patients done kidney transplantation or renal replacement therapy before 58 years old; one of family patients died of complications before 55 years old; the patient with total kidney volume more than 650ml; the patient with total kidney volume increase rate more than 6% every year; the patient's PKD1 mutation belongs to truncated gene mutation.
• Both husband and wife have assisted reproductive conditions and will
• Pregnancy compliance with Chinese laws
• Signed informed consent

Exclusion Criteria:

• Active pathogenic microorganism infection, such as hepatitis B or C, HIV, pulmonary tuberculosis, giant cell virus, fungi or other contraindications for preimplantation genetic diagnosis and so on
• Any one of the couple has used any drugs which may lead to abnormal reproductive system function, reproductive cell abnormalities, pregnancy risk increases in the past 3 months, or has history of drug abuse
• Any one of the couple has malignancy
• The wife has uncontrolled hypertension or refractory hypertension
• The wife has diabetes mellitus
• The wife has albuminuria
• The wife has autoimmune disease
• The wife has other disorders or functional abnormalities, such as liver or renal dysfunction, which may be aggravated by pregnancy or assisted reproduction
• Allergy to drugs or related products which cannot avoid in our study
• Participating in other clinical studies in last 3 months
• Participants cannot follow the study program
• Other conditions that the researchers considered unsuitable for participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Preimplantation genetic diagnosis group; ADPKD patients will complete the whole process of preimplantation genetic diagnosis with healthy baby without pathogenic gene inheritance.	Procedure: Preimplantation Genetic Diagnosis; Using Preimplantation genetic diagnosis, including multiple annealing and looping-based amplification cycles amplification technique, the investigators have had screened out healthy embryos by In Vitro Fertilization. Then the investigators transplanted embryos returned to the parent. Finally, participants will have healthy baby without pathogenic gene inheritance.
No Intervention: Natural pregnancy group; ADPKD patients, pathogenic mutations in PKD1, have natural pregnancy without preimplantation genetic diagnosis.The investigators will perform genetic tests on the blood or umbilical cord blood of infants born between January 2014 and June 2020.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healthy baby Rate without pathogenic gene inheritance	The investigators will do umbilical cord blood gene detection for the baby to confirm with or without pathogenic gene inheritance. The investigators will compare two groups of healthy newborns rate.	through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate in pretest of preimplantation genetic diagnosis	Using couples blood to do pretest of preimplantation genetic diagnosis in Peripheral blood mononuclear lymphocyte.	through study completion, an average of 2 year
Technical failure rate of preimplantation genetic diagnosis.	The rate of amniotic fluid puncture test or umbilical cord blood gene detection confirm the offspring containing pathogenic gene mutation.	Amniotic fluid puncture test (pregnancy 16 to 19 weeks ) and Birth day
Oocyte retrieval rate	The proportion of good eggs obtained after ovulation induction	through study completion, an average of 2 years
Good quality embryo rate	The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection	through study completion, an average of 2 years
Pregnancy rate	Successful pregnancy rate of transplanted embryo	Four weeks after embryo transplantation
Take home baby rate	Healthy newborn birth rate in preimplantation genetic diagnosis group	Two week after neonatus birth day
The total kidney volume change rate	The investigators do twice kidney MRI scan for calculating total kidney volume change rate between enroll and postpartum 6 months.	From enroll to postpartum 6 months
The estimated glomerular filtration rate change	The investigators do twice serum creatinine test between enroll and postpartum 6 months, then using CKD-EPI formula to calculate eGFR.	From enroll to postpartum 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of ovarian hyperstimulation syndrome	the incidence of ovarian hyperstimulation syndrome	through study completion, an average of 2 years
The incidence of organ injuries	the incidence of organ injuries	through study completion, an average of 2 years
The incidence of infection	the incidence of infection	through study completion, an average of 2 years
The incidence of abortion rate	the incidence of abortion rate	through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Changlin Mei
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; The First Affiliated Hospital of Anhui Medical University; Xiangya Hospital of Central South University; LanZhou University; The Second Hospital of Hebei Medical University; Peking University Third Hospital; First Affiliated Hospital, Sun Yat-Sen University; Southwest Hospital, China; West China Hospital; Shengjing Hospital; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Shandong Provincial Hospital; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University; The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Zhengzhou University; Shaanxi Provincial People's Hospital; Wuhan Union Hospital, China; Renmin Hospital of Wuhan University; Tang-Du Hospital; Sir Run Run Shaw Hospital; Second Xiangya Hospital of Central South University; Reproductive & Genetic Hospital of CITIC-Xiangya; Hebei Medical University Third Hospital; Sichuan Provincial People's Hospital; Navy General Hospital, Beijing; Fuzhou General Hospital; Wuhan TongJi Hospital; West China Second University Hospital; Hebei Province Center for Reproductive Medicine; Hospital for Reproductive Medicine Affiliated to Shandong University
• Investigators: Principal Investigator: changlin Mei, Master, Institute of Nephrology, Changzheng Hospital; Principal Investigator: wen Li, doctor, Center of Reproductive Medicine, Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2016
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (Estimate): October 28, 2016

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Arthrogryposis
• Other Study ID Numbers: CZKIPLA-ADPKD-003

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
• product manufactured in and exported from the U.S.: No