Stem Cell Therapy Combined Hormone Replacement Therapy in Patients With Premature Ovarian Failure

Study Overview
=================
Brief Summary
-----------------
Premature ovarian failure (POF) refers the occurrence of amenorrhoea, elevated serum gonadotrophins and hypoestrogenism levels in female before the age of 40. It has important physical and psychological consequences/impact in those patients. Premature ovarian failure (POF) is currently managed by non-physiological sex steroid regimens which are inadequate at optimizing uterine characteristics. Human umbilical cord mesenchymal stem cells (hUCMSCs) and human cord blood mononuclear cells (hCBMNCs) have been shown to have the ability to modulate the immune response and enhance angiogenesis, suggesting the novel and promising therapeutic strategy for POF. In this study, the safety and efficacy of hUCMSCs and hCBMNCs transplantation combined with Hormone Replacement Therapy will be evaluated in patients with Premature Ovarian Failure. Participants will be followed for an expected average of 48 weeks.

Official Title
-----------------
A Phase Ι/Π Study of Human Cord Blood Mononuclear Cells and Human Umbilical Cord Mesenchymal Stem Cells Transplantation Combined With Hormone Replacement Therapy in Patients With Premature Ovarian Failure

Conditions
-----------------
Premature Ovarian Failure，

Intervention / Treatment
-----------------
* Biological: human umbilical cord mesenchymal stem cells
* Biological: hUCMSCs and hCBMNCs
* Biological: human cord blood mononuclear cells
* Drug: Hormone Replacement Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Between age 18- 39 years, Female only. Diagnosed with Premature Ovarian Failure，and currently receiving Hormone Replacement Therapy; Willing to sign the Informed Consent Form. Exclusion Criteria: Fragile X chromosome. polycystic ovary syndrome. HIV+. Autoimmune disease, e.g. lupus erythematosus, multiple sclerosis. Severe pulmonary and hematological disease, malignancy or hypo-immunity. Currently undertaking other treatment that may affect the safety/efficacy of stem cells. Pregnancy or lactation Enrollment in other trials in the last 3 months. • Other criteria the investigator consider improper for inclusion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group1 : HRT plus hUCMSCs treatment:<br>Participants will be given HRT plus human cord mesenchymal stem cells transplantation with a 12 menstrual Cycle follow-up. | Biological: human umbilical cord mesenchymal stem cells<br> <br> |
| Experimental: Group 2: HRT plus hCBMNCs and hUCMSCs therapy<br>Participants will be given HRT plus combination of hCBMNCs together with hUCMSCs transplantation with a 12 menstrual Cycle follow-up. | Biological: hUCMSCs and hCBMNCs<br> <br> |
| Experimental: Group3 : HRT plus hCBMNCs treatment:<br>Participants will be given HRT plus human cord blood mononuclear cells transplantation with a 12 menstrual Cycle follow-up. | Biological: human cord blood mononuclear cells<br> <br> |
| Experimental: Group 4:Hormone Replacement Therapy<br>Participants will be given conventional therapy only with a 12 menstrual Cycle follow-up. | Drug: Hormone Replacement Therapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Level of follicle-stimulating hormone |  | 48 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uterine and Ovary characteristics of B ultrasound， including Uterine/Ovarian size and Blood Flow |  | 48 weeks after treatment | 
| Modified Kupperman Score |  | 48 weeks after treatment | 
| Incidence of Adverse Events and Serious Adverse Events |  | 48 weeks after treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hormone Replacement Therapy，, Premature Ovarian Failure，, Stem Cell Therapy