Amnion Bilayer and Stem Cell Combination Therapy on Thin Endometrium Infertile Patients

NCT04676269 | Unknown Early Phase 1 DMC

• 1 other identifier: 19-10-1202
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Severe infections or trauma to the endometrial lining causes permanent scars that disrupt the menstrual cycle and lead to conceive failure. Transplantation of biological graft seeded with stem cells is purposed to regenerate and recover the capability of the endometrial lining back into its cycles. Initially, the techniques to isolate and culture the endometrial cells and amnion epithelial stem cells were developed, then the endometrial cells form patients with thin endometrium. Tissue were obtained from hysteroscopic biopsy, weight between 100 µl, while up to 20 µl from the thin endometrium. Tissue were digested using collagenase-1 and cultured using DMEM-F12 added wit epidermal growth factor. Endometrial cells will be characterized to SSUD2, ICAM and BRCP1. Amnion epithelial stem cells (hAESC) will be isolated using collagenase-1 and hyaluronidase. Characterization towards TRA-1-60, SSEA-4, Oct 3/4, and Nanog. In the future, the cells will be co-culture on amnion bilayer, and stained using IHC against α-cadherin, estrogen receptor α, progesterone receptor. Endometrial receptivity (HOXA10, LIF (early secretory) adhesion, VEGF, osteopontin (SPP1) to indicate the pinopodes will be identified using qPCR.The SPP1, target of MIR424 expressed during the receptive phase.

Conditions

Cell- and Tissue-Based Therapy

Keywords

Endometrial stem cells; Amnion epithelial stem cells; Amnion bilayer; Thin endometrium; Secondary amenorrhoe

Outcome Measures

Primary Outcomes (2)

• Change in endometrium thickness

  Observation by USG

  7 and 14 days after amnion bilayer seeded with endometrial cells co-cultured with hAESC is transplanted into patient' womb

• Change in amenorrhea severity

  Patients' report

  7 and 14 days after amnion bilayer seeded with endometrial cells co-cultured with hAESC is transplanted into patient' womb

Study Arms (4)

Amnion only

SHAM COMPARATOR

Amnion bilayer as a scaffold to overlay the endometrium, with minor curettage prior to stick the scaffold.

Biological: Amnion only

Amnion- self endometrium stem cells (EnSC)

EXPERIMENTAL

Amnion bilayer as a scaffold, seeded with endometrium stem cells to regenerate the thin endometrium.

Biological: Amnion - endometrium cells

Amnion- amnion epithelial stem cells (AESC)

EXPERIMENTAL

Amnion bilayer as a scaffold, seeded with amnion epithelial stem cells to regenerate the thin endometrium.

Biological: Amnion - amnion epithelial cells

Amnion- co culture self EnSC - AESC

EXPERIMENTAL

Amnion bilayer as a scaffold, seeded with co-culture of endometrium stem cells and amnion epithelial stem cells to regenerate the thin endometrium.

Biological: Amnion-EnSC-AESC

Interventions

Amnion only BIOLOGICAL

Patients endometrium will be transplanted with amnion only (without seeded cells)

Amnion only

Amnion - endometrium cells BIOLOGICAL

Patients endometrium will be transplanted with amnion seeded with endometrium cells isolated from the patients themselves

Amnion- self endometrium stem cells (EnSC)

Amnion - amnion epithelial cells BIOLOGICAL

Patients endometrium will be transplanted with amnion seeded with amnion epithelial stem cells isolated from other patients' caesarean sectio amnion membrane (tested HLA-DR negative to prevent rejection)

Amnion- amnion epithelial stem cells (AESC)

Amnion-EnSC-AESC BIOLOGICAL

Patients endometrium will be transplanted with amnion seeded with endometrium cells-amnion epithelial stem cells co-culture

Amnion- co culture self EnSC - AESC

Eligibility Criteria

• Age: Up to 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with thin endometrium without scar
• Patients with acute thin endometrium post-therapy (medicamentosa)
• Patients who are willing to participate in the study

You may not qualify if:

• Patients with thin endometrium due to TB
• Patients with cancer in the reproductive system

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

RSUPN Cipto Mangunkusumo

Jakarta Pusat, DKI Jakarta, 10430, Indonesia

RECRUITING

Study Officials

• Achmad Kemal Harzif, MD

  Faculty of Medicine, Indonesia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Achmad Kemal Harzif, MD

CONTACT

+62 813-1586-6390; kemal.achmad@gmail.com

Normalina Sandora, PhD

CONTACT

+62 812-9896-3425; normalinasandora@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: None of the participants, gynecologists, statistician, nurses nor of the participant' partners are informed about the treatment groups.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 21, 2020
• Study Start: December 9, 2019
• Primary Completion: July 15, 2021
• Study Completion: December 15, 2021
• Last Updated: December 21, 2020

Record last verified: 2020-12

Locations

ID (1)