## Protocol Section
### Identification Module
**NCT ID:** NCT02948179

**Acronym:** ESPERANCE

**Brief Title:** 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

#### Organization Study ID Info
**ID:** CZKIPLA-ADPKD-003
#### Organization
**Class:** OTHER
**Full Name:** Shanghai Changzheng Hospital
### Status Module
#### Completion Date
**Date:** 2020-12-31

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2021-01-26

**Type:** ACTUAL

**Last Update Submit Date:** 2021-01-25

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2020-11-30

**Type:** ACTUAL

#### Start Date
**Date:** 2016-09-02

**Type:** ACTUAL

**Status Verified Date:** 2021-01

#### Study First Post Date
**Date:** 2016-10-28
**Type:** ESTIMATED
**Study First Submit Date:** 2016-10-20
**Study First Submit QC Date:** 2016-10-26
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** The First Affiliated Hospital of Anhui Medical University

**Class:** OTHER

**Name:** The First Affiliated Hospital with Nanjing Medical University

**Class:** OTHER_GOV

**Name:** Shandong Provincial Hospital

**Class:** OTHER

**Name:** Tang-Du Hospital

**Class:** OTHER

**Name:** Shengjing Hospital

**Class:** OTHER

**Name:** Second Xiangya Hospital of Central South University

**Class:** OTHER

**Name:** Reproductive & Genetic Hospital of CITIC-Xiangya

**Class:** OTHER

**Name:** Peking University Third Hospital

**Class:** OTHER

**Name:** Navy General Hospital, Beijing

**Class:** OTHER

**Name:** The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

**Class:** OTHER

**Name:** The First Affiliated Hospital of Soochow University

**Class:** OTHER

**Name:** Sir Run Run Shaw Hospital

**Class:** OTHER

**Name:** Fuzhou General Hospital

**Class:** OTHER

**Name:** The First Affiliated Hospital of Zhengzhou University

**Class:** OTHER

**Name:** Wuhan TongJi Hospital

**Class:** OTHER

**Name:** Wuhan Union Hospital, China

**Class:** OTHER

**Name:** Renmin Hospital of Wuhan University

**Class:** OTHER

**Name:** Xiangya Hospital of Central South University

**Class:** OTHER

**Name:** First Affiliated Hospital, Sun Yat-Sen University

**Class:** OTHER

**Name:** Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

**Class:** OTHER

**Name:** Southwest Hospital, China

**Class:** OTHER

**Name:** LanZhou University

**Class:** OTHER

**Name:** Shaanxi Provincial People's Hospital

**Class:** OTHER

**Name:** West China Hospital

**Class:** OTHER

**Name:** West China Second University Hospital

**Class:** OTHER

**Name:** Sichuan Provincial People's Hospital

**Class:** OTHER

**Name:** Hebei Medical University Third Hospital

**Class:** UNKNOWN

**Name:** Hebei Province Center for Reproductive Medicine

**Class:** OTHER

**Name:** The Second Hospital of Hebei Medical University

**Class:** UNKNOWN

**Name:** Hospital for Reproductive Medicine Affiliated to Shandong University

#### Lead Sponsor

**Class:** OTHER

**Name:** Changlin Mei

#### Responsible Party

**Investigator Affiliation:** Shanghai Changzheng Hospital

**Investigator Full Name:** Changlin Mei

**Investigator Title:** Professor, Director of kidney Institute

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Polycystic Kidney, Type 1 Autosomal Dominant Disease

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 459

**Type:** ACTUAL

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** ADPKD patients will complete the whole process of preimplantation genetic diagnosis with healthy baby without pathogenic gene inheritance.

**Intervention Names:**

- Procedure: Preimplantation Genetic Diagnosis

**Label:** Preimplantation genetic diagnosis group

**Type:** EXPERIMENTAL

#### Arm Group 2

**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.

**Label:** Natural pregnancy group

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Preimplantation genetic diagnosis group

**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.

**Name:** Preimplantation Genetic Diagnosis

**Type:** PROCEDURE

### Outcomes Module

#### Other Outcomes

**Description:** the incidence of ovarian hyperstimulation syndrome

**Measure:** The incidence of ovarian hyperstimulation syndrome

**Time Frame:** through study completion, an average of 2 years

**Description:** the incidence of organ injuries

**Measure:** The incidence of organ injuries

**Time Frame:** through study completion, an average of 2 years

**Description:** the incidence of infection

**Measure:** The incidence of infection

**Time Frame:** through study completion, an average of 2 years

**Description:** the incidence of abortion rate

**Measure:** The incidence of abortion rate

**Time Frame:** through study completion, an average of 2 years

#### Primary Outcomes

**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.

**Measure:** Healthy baby Rate without pathogenic gene inheritance

**Time Frame:** through study completion, an average of 2 year

#### Secondary Outcomes

**Description:** Using couples blood to do pretest of preimplantation genetic diagnosis in Peripheral blood mononuclear lymphocyte.

**Measure:** Success rate in pretest of preimplantation genetic diagnosis

**Time Frame:** through study completion, an average of 2 year

**Description:** The rate of amniotic fluid puncture test or umbilical cord blood gene detection confirm the offspring containing pathogenic gene mutation.

**Measure:** Technical failure rate of preimplantation genetic diagnosis.

**Time Frame:** Amniotic fluid puncture test (pregnancy 16 to 19 weeks ) and Birth day

**Description:** The proportion of good eggs obtained after ovulation induction

**Measure:** Oocyte retrieval rate

**Time Frame:** through study completion, an average of 2 years

**Description:** The well-developed blastocyst ratio obtained after intracytoplasmic sperm injection

**Measure:** Good quality embryo rate

**Time Frame:** through study completion, an average of 2 years

**Description:** Successful pregnancy rate of transplanted embryo

**Measure:** Pregnancy rate

**Time Frame:** Four weeks after embryo transplantation

**Description:** Healthy newborn birth rate in preimplantation genetic diagnosis group

**Measure:** Take home baby rate

**Time Frame:** Two week after neonatus birth day

**Description:** The investigators do twice kidney MRI scan for calculating total kidney volume change rate between enroll and postpartum 6 months.

**Measure:** The total kidney volume change rate

**Time Frame:** From enroll to postpartum 6 months

**Description:** The investigators do twice serum creatinine test between enroll and postpartum 6 months, then using CKD-EPI formula to calculate eGFR.

**Measure:** The estimated glomerular filtration rate change

**Time Frame:** From enroll to postpartum 6 months

### Eligibility Module

**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

**Maximum Age:** 35 Years

**Minimum Age:** 20 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Hefei

**Country:** China

**Facility:** The First Affiliated Hospital of Anhui Medical University

**State:** Anhui

**Zip:** 230000

**Location 2:**

**City:** Beijing

**Country:** China

**Facility:** Navy General Hospital

**State:** Beijing

**Zip:** 100000

**Location 3:**

**City:** Beijing

**Country:** China

**Facility:** Peking University Third Hospital

**State:** Beijing

**Zip:** 100000

**Location 4:**

**City:** Chongqing

**Country:** China

**Facility:** Southwest Hospital

**State:** Chongqing

**Zip:** 400000

**Location 5:**

**City:** Fuzhou

**Country:** China

**Facility:** Fuzhou General Hospital

**State:** Fujian

**Zip:** 350000

**Location 6:**

**City:** Lanzhou

**Country:** China

**Facility:** The First Hospital of Lanzhou University

**State:** Gansu

**Zip:** 730000

**Location 7:**

**City:** Guangzhou

**Country:** China

**Facility:** Sun Yat-sen Memorial Hospital of Sun Yat-sen University

**State:** Guangdong

**Zip:** 510000

**Location 8:**

**City:** Guangzhou

**Country:** China

**Facility:** The First Affiliated Hospital of Sun Yat-sen University

**State:** Guangdong

**Zip:** 510000

**Location 9:**

**City:** Shijiazhuang

**Country:** China

**Facility:** Hebei Province Center for Reproductive Medicine

**State:** Hebei

**Zip:** 050000

**Location 10:**

**City:** Shijiazhuang

**Country:** China

**Facility:** The Second Hospital of Hebei Medical University

**State:** Hebei

**Zip:** 050000

**Location 11:**

**City:** Shijiazhuang

**Country:** China

**Facility:** The Third Hospital of Hebei Medical University

**State:** Hebei

**Zip:** 050000

**Location 12:**

**City:** Zhengzhou

**Country:** China

**Facility:** The First Affiliated Hospital of Zhengzhou University

**State:** Henan

**Zip:** 450000

**Location 13:**

**City:** Wuhan

**Country:** China

**Facility:** Renmin Hospital of Wuhan University

**State:** Hubei

**Zip:** 430000

**Location 14:**

**City:** Wuhan

**Country:** China

**Facility:** Wuhan Tongji Hospital

**State:** Hubei

**Zip:** 430000

**Location 15:**

**City:** Wuhan

**Country:** China

**Facility:** Wuhan Union Hospital

**State:** Hubei

**Zip:** 430000

**Location 16:**

**City:** Changsha

**Country:** China

**Facility:** Reproductive & Genetic Hospital of CITIC-Xiangya

**State:** Hunan

**Zip:** 410000

**Location 17:**

**City:** Changsha

**Country:** China

**Facility:** Second Xiangya Hospital of Central South University

**State:** Hunan

**Zip:** 410000

**Location 18:**

**City:** Changsha

**Country:** China

**Facility:** Xiangya Hospital of Central South University

**State:** Hunan

**Zip:** 410000

**Location 19:**

**City:** Nanjing

**Country:** China

**Facility:** The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

**State:** Jiangsu

**Zip:** 210000

**Location 20:**

**City:** Nanjing

**Country:** China

**Facility:** The First Affiliated Hospital with Nanjing Medical University

**State:** Jiangsu

**Zip:** 210000

**Location 21:**

**City:** Suzhou

**Country:** China

**Facility:** The First Affiliated Hospital of Soochow University

**State:** Jiangsu

**Zip:** 215000

**Location 22:**

**City:** Shenyang

**Country:** China

**Facility:** Shengjing Hospital

**State:** Liaoning

**Zip:** 110000

**Location 23:**

**City:** Jinan

**Country:** China

**Facility:** Hospital for Reproductive Medicine Affiliated to Shandong University

**State:** Shandong

**Zip:** 250000

**Location 24:**

**City:** Jinan

**Country:** China

**Facility:** Shandong Provincial Hospital

**State:** Shandong

**Zip:** 250000

**Location 25:**

**City:** Shanghai

**Country:** China

**Facility:** Shanghai Changzheng Hospital

**State:** Shanghai

**Zip:** 200000

**Location 26:**

**City:** Taiyuan

**Country:** China

**Facility:** Shanxi Provincial People's Hospital

**State:** Shanxi

**Zip:** 030000

**Location 27:**

**City:** Xi'an

**Country:** China

**Facility:** Tang-Du Hospital

**State:** Shanxi

**Zip:** 710000

**Location 28:**

**City:** Chengdu

**Country:** China

**Facility:** Shanxi Provincial People's Hospital

**State:** Sichuan

**Zip:** 610000

**Location 29:**

**City:** Chengdu

**Country:** China

**Facility:** West China Hospital of Sichuan University

**State:** Sichuan

**Zip:** 610000

**Location 30:**

**City:** Chengdu

**Country:** China

**Facility:** West China Second University Hospital

**State:** Sichuan

**Zip:** 610000

**Location 31:**

**City:** Hangzhou

**Country:** China

**Facility:** Sir Run Run Shaw Hospital of Zhejiang University

**State:** Zhejiang

**Zip:** 310000

#### Overall Officials

**Official 1:**

**Affiliation:** Institute of Nephrology, Changzheng Hospital

**Name:** changlin Mei, Master

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Center of Reproductive Medicine, Changzheng Hospital

**Name:** wen Li, doctor

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000007592

- Term: Joint Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000009135

- Term: Muscular Diseases

- ID: D000009139

- Term: Musculoskeletal Abnormalities

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000052177

- Term: Kidney Diseases, Cystic

- ID: D000000015

- Term: Abnormalities, Multiple

- ID: D000072661

- Term: Ciliopathies

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10698

- Name: Kidney Diseases

- Relevance: HIGH

- As Found: Kidney Disease

- ID: M10712

- Name: Polycystic Kidney Diseases

- Relevance: HIGH

- As Found: Polycystic Kidney

- ID: M19237

- Name: Polycystic Kidney, Autosomal Dominant

- Relevance: HIGH

- As Found: Polycystic Kidney, Type 1 Autosomal Dominant Disease

- ID: M4484

- Name: Arthrogryposis

- Relevance: HIGH

- As Found: Autosomal Dominant

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10621

- Name: Joint Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12092

- Name: Muscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M12096

- Name: Musculoskeletal Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M26983

- Name: Kidney Diseases, Cystic

- Relevance: LOW

- As Found: Unknown

- ID: M14

- Name: Abnormalities, Multiple

- Relevance: LOW

- As Found: Unknown

- ID: M1076

- Name: Ciliopathies

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: T591

- Name: Autosomal Dominant Multiple Pterygium Syndrome

- Relevance: HIGH

- As Found: Autosomal Dominant

- ID: T493

- Name: Arthrogryposis Multiplex Congenita

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001176

- Term: Arthrogryposis

- ID: D000007674

- Term: Kidney Diseases

- ID: D000007690

- Term: Polycystic Kidney Diseases

- ID: D000016891

- Term: Polycystic Kidney, Autosomal Dominant

### Misc Info Module

- Version Holder: 2024-05-24
