Polycystic Kidney, Type 1 Autosomal Dominant Disease Clinical Trial
— ESPERANCEOfficial title:
Efficacy and Safety of Preimplantation Genetic Diagnosis in Blocking Pathogenic Gene Inheritance for Autosomal Dominant Polycystic Kidney Disease: a Multicenter Clinical Trial
| Verified date | January 2021 |
| Source | Shanghai Changzheng Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 459 |
| Est. completion date | December 31, 2020 |
| Est. primary completion date | November 30, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 20 Years to 35 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| China | Navy General Hospital | Beijing | Beijing |
| China | Peking University Third Hospital | Beijing | Beijing |
| China | Reproductive & Genetic Hospital of CITIC-Xiangya | Changsha | Hunan |
| China | Second Xiangya Hospital of Central South University | Changsha | Hunan |
| China | Xiangya Hospital of Central South University | Changsha | Hunan |
| China | Shanxi Provincial People's Hospital | Chengdu | Sichuan |
| China | West China Hospital of Sichuan University | Chengdu | Sichuan |
| China | West China Second University Hospital | Chengdu | Sichuan |
| China | Southwest Hospital | Chongqing | Chongqing |
| China | Fuzhou General Hospital | Fuzhou | Fujian |
| China | Sun Yat-sen Memorial Hospital of Sun Yat-sen University | Guangzhou | Guangdong |
| China | The First Affiliated Hospital of Sun Yat-sen University | Guangzhou | Guangdong |
| China | Sir Run Run Shaw Hospital of Zhejiang University | Hangzhou | Zhejiang |
| China | The First Affiliated Hospital of Anhui Medical University | Hefei | Anhui |
| China | Hospital for Reproductive Medicine Affiliated to Shandong University | Jinan | Shandong |
| China | Shandong Provincial Hospital | Jinan | Shandong |
| China | The First Hospital of Lanzhou University | Lanzhou | Gansu |
| China | The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School | Nanjing | Jiangsu |
| China | The First Affiliated Hospital with Nanjing Medical University | Nanjing | Jiangsu |
| China | Shanghai Changzheng Hospital | Shanghai | Shanghai |
| China | Shengjing Hospital | Shenyang | Liaoning |
| China | Hebei Province Center for Reproductive Medicine | Shijiazhuang | Hebei |
| China | The Second Hospital of Hebei Medical University | Shijiazhuang | Hebei |
| China | The Third Hospital of Hebei Medical University | Shijiazhuang | Hebei |
| China | The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu |
| China | Shanxi Provincial People's Hospital | Taiyuan | Shanxi |
| China | Renmin Hospital of Wuhan University | Wuhan | Hubei |
| China | Wuhan Tongji Hospital | Wuhan | Hubei |
| China | Wuhan Union Hospital | Wuhan | Hubei |
| China | Tang-Du Hospital | Xi'an | Shanxi |
| China | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | Henan |
| Lead Sponsor | Collaborator |
|---|---|
| Changlin Mei | First Affiliated Hospital, Sun Yat-Sen University, Fuzhou General Hospital, Hebei Medical University Third Hospital, Hebei Province Center for Reproductive Medicine, Hospital for Reproductive Medicine Affiliated to Shandong University, LanZhou University, Navy General Hospital, Peking University Third Hospital, Renmin Hospital of Wuhan University, Reproductive & Genetic Hospital of CITIC-Xiangya, Second Xiangya Hospital of Central South University, Shaanxi Provincial People's Hospital, Shandong Provincial Hospital, Shengjing Hospital, Sichuan Provincial People's Hospital, Sir Run Run Shaw Hospital, Southwest Hospital, China, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Tang-Du Hospital, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, The First Affiliated Hospital of Anhui Medical University, The First Affiliated Hospital of Soochow University, The First Affiliated Hospital of Zhengzhou University, The First Affiliated Hospital with Nanjing Medical University, The Second Hospital of Hebei Medical University, West China Hospital, West China Second University Hospital, Wuhan TongJi Hospital, Wuhan Union Hospital, China, Xiangya Hospital of Central South University |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | The incidence of ovarian hyperstimulation syndrome | the incidence of ovarian hyperstimulation syndrome | through study completion, an average of 2 years | |
| Other | The incidence of organ injuries | the incidence of organ injuries | through study completion, an average of 2 years | |
| Other | The incidence of infection | the incidence of infection | through study completion, an average of 2 years | |
| Other | The incidence of abortion rate | the incidence of abortion rate | through study completion, an average of 2 years | |
| Primary | 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 | 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 | |
| Secondary | 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 | |
| Secondary | Oocyte retrieval rate | The proportion of good eggs obtained after ovulation induction | through study completion, an average of 2 years | |
| Secondary | Good quality embryo rate | The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection | through study completion, an average of 2 years | |
| Secondary | Pregnancy rate | Successful pregnancy rate of transplanted embryo | Four weeks after embryo transplantation | |
| Secondary | Take home baby rate | Healthy newborn birth rate in preimplantation genetic diagnosis group | Two week after neonatus birth day | |
| Secondary | 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 | |
| Secondary | 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 |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT02055079 -
Pulsed Oral Sirolimus in Autosomal Dominant Polycystic Kidney Disease
|
Phase 3 |