Back to resultsUsing Preimplantation Genetic Diagnosis in Autosomal Dominant Polycystic Kidney Disease Patients: a Multicenter Clinical Trial (ESPERANCE)
Primary Purpose
Polycystic Kidney, Type 1 Autosomal Dominant Disease
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Preimplantation Genetic Diagnosis
Sponsored by
About this trial
This is an interventional prevention trial for Polycystic Kidney, Type 1 Autosomal Dominant Disease
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
Sites / Locations
- The First Affiliated Hospital of Anhui Medical University
- Navy General Hospital
- Peking University Third Hospital
- Southwest Hospital
- Fuzhou General Hospital
- The First Hospital of Lanzhou University
- Sun Yat-sen Memorial Hospital of Sun Yat-sen University
- The First Affiliated Hospital of Sun Yat-sen University
- Hebei Province Center for Reproductive Medicine
- The Second Hospital of Hebei Medical University
- The Third Hospital of Hebei Medical University
- The First Affiliated Hospital of Zhengzhou University
- Renmin Hospital of Wuhan University
- Wuhan Tongji Hospital
- Wuhan Union Hospital
- Reproductive & Genetic Hospital of CITIC-Xiangya
- Second Xiangya Hospital of Central South University
- Xiangya Hospital of Central South University
- The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
- The First Affiliated Hospital with Nanjing Medical University
- The First Affiliated Hospital of Soochow University
- Shengjing Hospital
- Hospital for Reproductive Medicine Affiliated to Shandong University
- Shandong Provincial Hospital
- Shanghai Changzheng Hospital
- Shanxi Provincial People's Hospital
- Tang-Du Hospital
- Shanxi Provincial People's Hospital
- West China Hospital of Sichuan University
- West China Second University Hospital
- Sir Run Run Shaw Hospital of Zhejiang University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Preimplantation genetic diagnosis group
Natural pregnancy group
Arm Description
ADPKD patients will complete the whole process of preimplantation genetic diagnosis with healthy baby without pathogenic gene inheritance.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Success rate in pretest of preimplantation genetic diagnosis
Using couples blood to do pretest of preimplantation genetic diagnosis in Peripheral blood mononuclear lymphocyte.
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.
Oocyte retrieval rate
The proportion of good eggs obtained after ovulation induction
Good quality embryo rate
The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection
Pregnancy rate
Successful pregnancy rate of transplanted embryo
Take home baby rate
Healthy newborn birth rate in preimplantation genetic diagnosis group
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.
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.
Full Information
NCT ID
NCT02948179
First Posted
October 20, 2016
Last Updated
January 25, 2021
Sponsor
Changlin Mei
Collaborators
The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital with Nanjing Medical University, Shandong Provincial Hospital, Tang-Du Hospital, Shengjing Hospital, Second Xiangya Hospital of Central South University, Reproductive & Genetic Hospital of CITIC-Xiangya, Peking University Third Hospital, Navy General Hospital, Beijing, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The First Affiliated Hospital of Soochow University, Sir Run Run Shaw Hospital, Fuzhou General Hospital, The First Affiliated Hospital of Zhengzhou University, Wuhan TongJi Hospital, Wuhan Union Hospital, China, Renmin Hospital of Wuhan University, Xiangya Hospital of Central South University, First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Southwest Hospital, China, LanZhou University, Shaanxi Provincial People's Hospital, West China Hospital, West China Second University Hospital, Sichuan Provincial People's Hospital, Hebei Medical University Third Hospital, Hebei Province Center for Reproductive Medicine, The Second Hospital of Hebei Medical University, Hospital for Reproductive Medicine Affiliated to Shandong University
1. Study Identification
Unique Protocol Identification Number
NCT02948179
Brief Title
Using Preimplantation Genetic Diagnosis in Autosomal Dominant Polycystic Kidney Disease Patients: a Multicenter Clinical Trial
Acronym
ESPERANCE
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
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
September 2, 2016 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Changlin Mei
Collaborators
The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital with Nanjing Medical University, Shandong Provincial Hospital, Tang-Du Hospital, Shengjing Hospital, Second Xiangya Hospital of Central South University, Reproductive & Genetic Hospital of CITIC-Xiangya, Peking University Third Hospital, Navy General Hospital, Beijing, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The First Affiliated Hospital of Soochow University, Sir Run Run Shaw Hospital, Fuzhou General Hospital, The First Affiliated Hospital of Zhengzhou University, Wuhan TongJi Hospital, Wuhan Union Hospital, China, Renmin Hospital of Wuhan University, Xiangya Hospital of Central South University, First Affiliated Hospital, Sun Yat-Sen University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Southwest Hospital, China, LanZhou University, Shaanxi Provincial People's Hospital, West China Hospital, West China Second University Hospital, Sichuan Provincial People's Hospital, Hebei Medical University Third Hospital, Hebei Province Center for Reproductive Medicine, The Second Hospital of Hebei Medical University, Hospital for Reproductive Medicine Affiliated to Shandong University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Kidney, Type 1 Autosomal Dominant Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
459 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Preimplantation genetic diagnosis group
Arm Type
Experimental
Arm Description
ADPKD patients will complete the whole process of preimplantation genetic diagnosis with healthy baby without pathogenic gene inheritance.
Arm Title
Natural pregnancy group
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Preimplantation Genetic Diagnosis
Intervention Description
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.
Primary Outcome Measure Information:
Title
Healthy baby Rate without pathogenic gene inheritance
Description
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.
Time Frame
through study completion, an average of 2 year
Secondary Outcome Measure Information:
Title
Success rate in pretest of preimplantation genetic diagnosis
Description
Using couples blood to do pretest of preimplantation genetic diagnosis in Peripheral blood mononuclear lymphocyte.
Time Frame
through study completion, an average of 2 year
Title
Technical failure rate of preimplantation genetic diagnosis.
Description
The rate of amniotic fluid puncture test or umbilical cord blood gene detection confirm the offspring containing pathogenic gene mutation.
Time Frame
Amniotic fluid puncture test (pregnancy 16 to 19 weeks ) and Birth day
Title
Oocyte retrieval rate
Description
The proportion of good eggs obtained after ovulation induction
Time Frame
through study completion, an average of 2 years
Title
Good quality embryo rate
Description
The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection
Time Frame
through study completion, an average of 2 years
Title
Pregnancy rate
Description
Successful pregnancy rate of transplanted embryo
Time Frame
Four weeks after embryo transplantation
Title
Take home baby rate
Description
Healthy newborn birth rate in preimplantation genetic diagnosis group
Time Frame
Two week after neonatus birth day
Title
The total kidney volume change rate
Description
The investigators do twice kidney MRI scan for calculating total kidney volume change rate between enroll and postpartum 6 months.
Time Frame
From enroll to postpartum 6 months
Title
The estimated glomerular filtration rate change
Description
The investigators do twice serum creatinine test between enroll and postpartum 6 months, then using CKD-EPI formula to calculate eGFR.
Time Frame
From enroll to postpartum 6 months
Other Pre-specified Outcome Measures:
Title
The incidence of ovarian hyperstimulation syndrome
Description
the incidence of ovarian hyperstimulation syndrome
Time Frame
through study completion, an average of 2 years
Title
The incidence of organ injuries
Description
the incidence of organ injuries
Time Frame
through study completion, an average of 2 years
Title
The incidence of infection
Description
the incidence of infection
Time Frame
through study completion, an average of 2 years
Title
The incidence of abortion rate
Description
the incidence of abortion rate
Time Frame
through study completion, an average of 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
changlin Mei, Master
Organizational Affiliation
Institute of Nephrology, Changzheng Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
wen Li, doctor
Organizational Affiliation
Center of Reproductive Medicine, Changzheng Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The First Affiliated Hospital of Anhui Medical University
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230000
Country
China
Facility Name
Navy General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100000
Country
China
Facility Name
Peking University Third Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100000
Country
China
Facility Name
Southwest Hospital
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400000
Country
China
Facility Name
Fuzhou General Hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350000
Country
China
Facility Name
The First Hospital of Lanzhou University
City
Lanzhou
State/Province
Gansu
ZIP/Postal Code
730000
Country
China
Facility Name
Sun Yat-sen Memorial Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
The First Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
Hebei Province Center for Reproductive Medicine
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Facility Name
The Second Hospital of Hebei Medical University
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Facility Name
The Third Hospital of Hebei Medical University
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050000
Country
China
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450000
Country
China
Facility Name
Renmin Hospital of Wuhan University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Facility Name
Wuhan Tongji Hospital
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Facility Name
Wuhan Union Hospital
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430000
Country
China
Facility Name
Reproductive & Genetic Hospital of CITIC-Xiangya
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410000
Country
China
Facility Name
Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410000
Country
China
Facility Name
Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410000
Country
China
Facility Name
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Facility Name
The First Affiliated Hospital with Nanjing Medical University
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210000
Country
China
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215000
Country
China
Facility Name
Shengjing Hospital
City
Shenyang
State/Province
Liaoning
ZIP/Postal Code
110000
Country
China
Facility Name
Hospital for Reproductive Medicine Affiliated to Shandong University
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250000
Country
China
Facility Name
Shandong Provincial Hospital
City
Jinan
State/Province
Shandong
ZIP/Postal Code
250000
Country
China
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200000
Country
China
Facility Name
Shanxi Provincial People's Hospital
City
Taiyuan
State/Province
Shanxi
ZIP/Postal Code
030000
Country
China
Facility Name
Tang-Du Hospital
City
Xi'an
State/Province
Shanxi
ZIP/Postal Code
710000
Country
China
Facility Name
Shanxi Provincial People's Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Facility Name
West China Hospital of Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Facility Name
West China Second University Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Facility Name
Sir Run Run Shaw Hospital of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Using Preimplantation Genetic Diagnosis in Autosomal Dominant Polycystic Kidney Disease Patients: a Multicenter Clinical Trial
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