Clinical trial NCT02948179: Using Preimplantation Genetic Diagnosis in Autosomal Dominant Polycystic Kidney Disease Patients: a Multicenter Clinical Trial
Official title: Efficacy and Safety of Preimplantation Genetic Diagnosis in Blocking Pathogenic Gene Inheritance for Autosomal Dominant Polycystic Kidney Disease: a Multicenter Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Kidney, Type 1 Autosomal Dominant Disease
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
Collaborators: name: The First Affiliated Hospital of Anhui Medical University
name: The First Affiliated Hospital with Nanjing Medical University
name: Shandong Provincial Hospital
name: Tang-Du Hospital
name: Shengjing Hospital
name: Second Xiangya Hospital of Central South University
name: Reproductive & Genetic Hospital of CITIC-Xiangya
name: Peking University Third Hospital
name: Navy General Hospital, Beijing
name: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
name: The First Affiliated Hospital of Soochow University
name: Sir Run Run Shaw Hospital
name: Fuzhou General Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Wuhan TongJi Hospital
name: Wuhan Union Hospital, China
name: Renmin Hospital of Wuhan University
name: Xiangya Hospital of Central South University
name: First Affiliated Hospital, Sun Yat-Sen University
name: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Southwest Hospital, China
name: LanZhou University
name: Shaanxi Provincial People's Hospital
name: West China Hospital
name: West China Second University Hospital
name: Sichuan Provincial People's Hospital
name: Hebei Medical University Third Hospital
name: Hebei Province Center for Reproductive Medicine
name: The Second Hospital of Hebei Medical University
name: Hospital for Reproductive Medicine Affiliated to Shandong University
First posted: 2016-10-28
Enrollment: 459
Sex: ALL
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Healthy baby Rate without pathogenic gene inheritance
timeFrame: through study completion, an average of 2 year
Secondary outcomes:
measure: Success rate in pretest of preimplantation genetic diagnosis
timeFrame: through study completion, an average of 2 year
measure: Technical failure rate of preimplantation genetic diagnosis.
timeFrame: Amniotic fluid puncture test (pregnancy 16 to 19 weeks ) and Birth day
measure: Oocyte retrieval rate
timeFrame: through study completion, an average of 2 years
measure: Good quality embryo rate
timeFrame: through study completion, an average of 2 years
measure: Pregnancy rate
timeFrame: Four weeks after embryo transplantation
measure: Take home baby rate
timeFrame: Two week after neonatus birth day
measure: The total kidney volume change rate
timeFrame: From enroll to postpartum 6 months
measure: The estimated glomerular filtration rate change
timeFrame: From enroll to postpartum 6 months
Other outcomes:
measure: The incidence of ovarian hyperstimulation syndrome
timeFrame: through study completion, an average of 2 years
measure: The incidence of organ injuries
timeFrame: through study completion, an average of 2 years
measure: The incidence of infection
timeFrame: through study completion, an average of 2 years
measure: The incidence of abortion rate
timeFrame: through study completion, an average of 2 years
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Navy General Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Chongqing
country: China
facility: Southwest Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fuzhou General Hospital
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital of Sun Yat-sen University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Shijiazhuang
country: China
facility: Hebei Province Center for Reproductive Medicine
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Wuhan Tongji Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan Union Hospital
state: Hubei
city: Changsha
country: China
facility: Reproductive & Genetic Hospital of CITIC-Xiangya
state: Hunan
city: Changsha
country: China
facility: Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Nanjing
country: China
facility: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Shenyang
country: China
facility: Shengjing Hospital
state: Liaoning
city: Jinan
country: China
facility: Hospital for Reproductive Medicine Affiliated to Shandong University
state: Shandong
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Xi'an
country: China
facility: Tang-Du Hospital
state: Shanxi
city: Chengdu
country: China
facility: Shanxi Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: West China Second University Hospital
state: Sichuan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Institute of Nephrology, Changzheng Hospital
name: changlin Mei, Master
role: PRINCIPAL_INVESTIGATOR
affiliation: Center of Reproductive Medicine, Changzheng Hospital
name: wen Li, doctor
role: PRINCIPAL_INVESTIGATOR
References: