Treatment of Severe Asherman Syndrome by Collagen Scaffold Loaded With Autologous Bone Marrow Mononuclear Cells

• ClinicalTrials.gov Identifier: NCT02680366
• Recruitment Status: Unknown
• First Posted: February 11, 2016
• Last Update Posted: March 25, 2016
• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Information provided by (Responsible Party): Yali Hu, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study Description

Brief Summary:

This study evaluates the addition of collagen scaffold loaded with autologous bone marrow mononuclear cells(ABMNC) to Foley catheter balloon after hysteroscopic adhesiolysis in the treatment of severe asherman syndrome. Half of participants will receive collagen/ABMNC scaffold after hysteroscopic adhesiolysis, while the other half will receive Foley catheter balloon.

Condition or disease	Intervention/treatment	Phase
Infertility; Asherman Syndrome	Device: collagen/ABMNC scaffold; Device: Foley catheter balloon	Phase 2

Detailed Description:

Severe asherman syndrome will lead to infertility, and the most common method to treat asherman syndrome is operating to dissect adhesions. In order to prevent the postoperative re-adhesion, many physical isolation measures have been tried. However, they don't improve the microenvironment of endometrial regeneration. It's reported that bone marrow mononuclear cells have good effects on the functional recovery of injured uterus. This study will determine whether collagen scaffolds loaded with autologous bone marrow mononuclear cells will be more effective than Foley balloon catheters at treating infertile women with severe intrauterine adhesions who have taken hysteroscopic adhesiolysis. In addition, the study will be carried out in 2 centers, one is the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School, the other is Changzhou Maternal and Child Health Care Hospital that is in Jiangsu Province.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Single-blind, Controlled Clinical Trial of Treatment of Severe Asherman Syndrome by Collagen Scaffold Loaded With Autologous Bone Marrow Mononuclear Cells
• Study Start Date: February 2016
• Estimated Primary Completion Date: December 2018
• Estimated Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: collagen/ABMNC scaffold; collagen/ABMNC scaffold covered on Foley catheter balloon inserted after hysteroscopic adhesiolysis	Device: collagen/ABMNC scaffold; The patients will receive a bone marrow puncture to collect bone marrow cells which are used to isolation of ABMNCs. After that, hysteroscopic adhesiolysis will be done according to the patient's uterine adhesion. Then, the collagen/ABMNCs scaffold was covered on a Foley catheter balloon and placed into the uterine cavity. The catheter balloon was kept for 24 hours and then removed. Oral antibiotics were given to prevent infection in the second and third days after operation. 72 hours after the surgery, a vaginal speculum examinations will be done in order to make patients unknown about their arms. Estrogen will be administrated for 3 cycles to support the endometrial regeneration after the surgery. The clinical follow up will be done at 1, 3 and 6 months after the procedure.
Active Comparator: Foley catheter balloon; Foley catheter balloon inserted after hysteroscopic adhesiolysis	Device: Foley catheter balloon; The patients will receive a sham bone marrow puncture which just has a local anesthesia and collects no bone marrow cells to isolation. After that, hysteroscopic adhesiolysis will be done according to the patient's uterine adhesion. And then, a Foley catheter balloon will be placed into the uterine cavity and kept for 72 hours before it is removed. Oral antibiotics were given to prevent infection in the second and third days after operation. Estrogen will be administrated for 3 cycles to support the endometrial regeneration after the surgery. The clinical follow up will be done at 1, 3 and 6 months after the procedure.

Outcome Measures

Primary Outcome Measures :

1. Persistent pregnancy rate [ Time Frame: up to 24 months ]
   A successful clinical pregnancy means that at the 12th week of pregnancy, ultrasound reveals that the fetus had a heart activity and the size of the fetus is in consistent with the gestational week.

Secondary Outcome Measures :

1. Menstrual blood volume [ Time Frame: at 3 and 6 months ]
   Understanding the menstrual blood volume after surgery by the number of sanitary napkins per day and number of days, which will be compared with pre-operation.
2. Endometrial thickness [ Time Frame: at 1, 3 and 6 months ]
   Measure the endometrial thickness during ovulation by ultrasound by the same trained medical sonographers at 1, 3 and 6 months after surgery, comparing with pre-operation.
3. Endometrial blood supply [ Time Frame: at 1, 3 and 6 months ]
   Measure the endometrial blood supply during ovulation by ultrasound by the same trained medical sonographers at 1, 3 and 6 months after surgery, comparing with pre-operation.
4. Reduction of intrauterine scar area [ Time Frame: up to 3 month ]
   Evaluating the reduction of scar and its area by hysteroscopy compared with pre-operation.
5. Miscarriage rate [ Time Frame: up to 24 months ]
6. placenta adhesion rate [ Time Frame: up to 24 months ]
7. live- birth rate [ Time Frame: up to 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 40 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Having a clear desire to fertility;
• Infertility that is defined as a women fails to become pregnant after having a normal sex life for two years without contraception.
• Hysteroscopy examination confirmed intrauterine adhesions(patients who has at least one of the three symptoms which are amenorrhea, hypomenorrhea or infertility, and hysteroscopy or histologic diagnosis of intrauterine adhesions), meeting American Fertility Society diagnostic criteria Ⅱ-III;
• Normal ovarian function;
• Regular Menstrual cycles and menstruation is normal before abortion or curettage;
• BMI< 30 kg/m2;
• Sign a consent form;
• Follow the test plan and follow-up process.

Exclusion Criteria:

• Hereditary diseases;
• Simple thin endometrium with no uterine cavity adhesion;
• Simple Uterine scar formation with no uterine cavity adhesion after hysteroscopic adhesiolysis;
• Contraindications to bone marrow collection or assisted reproductive technology;
• History of malignant tumor;
• Other diseases associated with the uterus: uterine fibroids, severe adenomyosis, severe malformations of the uterus;
• Abnormal blood coagulation, liver and kidney dysfunction, or other diseases which the researchers think may affect the study(such as: uncontrolled hypertension, diabetes, sexually transmitted diseases);
• With a positive urine pregnancy test；
• Participating in other clinical studies at the same time;
• Hysteroscopic adhesiolysis more than 3 times in the past.

Contacts and Locations

Contacts

Contact: Yali Hu, MD,PhD; 02583304616 ext 66808; glyyhuyali@163.com

Locations

China, Jiangsu

Nanjing Drum Tower Hospital; Recruiting

Nanjing, Jiangsu, China, 210008

Contact: Yali Hu, MD,PhD 02583304616 ext 66808 glyyhuyali@163.com

Sponsors and Collaborators

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Investigators

• Principal Investigator: Yali Hu, MD,PhD; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

More Information

• Responsible Party: Yali Hu, MD,PhD, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• ClinicalTrials.gov Identifier: NCT02680366
• Other Study ID Numbers: 201600301
• First Posted: February 11, 2016
• Last Update Posted: March 25, 2016
• Last Verified: March 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Infertility; Gynatresia; Syndrome; Disease; Pathologic Processes