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Human iPSC for Repair of Vasodegenerative Vessels in Diabetic Retinopathy (iPSC)

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ClinicalTrials.gov Identifier: NCT03403699
Recruitment Status : Recruiting
First Posted : January 19, 2018
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Maria Grant, University of Alabama at Birmingham

Tracking Information
First Submitted Date January 11, 2018
First Posted Date January 19, 2018
Last Update Posted Date February 15, 2019
Actual Study Start Date January 11, 2018
Estimated Primary Completion Date January 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 11, 2018)
  • Generating iPSCs from peripheral blood [ Time Frame: From blood draw to 4 months ]
    Blood will be collected from the patient and cells will be isolated and shipped to ALSTEM for generation of iPSCs
  • Differentiate iPSCs into CD34+ cells and mesoderm [ Time Frame: 4 months to 4 years ]
    Specific cell culture conditions will be used to differentiate the cells into these two distinct populations
Original Primary Outcome Measures Same as current
Change History Complete list of historical versions of study NCT03403699 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Human iPSC for Repair of Vasodegenerative Vessels in Diabetic Retinopathy
Official Title Human iPSC for Repair of Vasodegenerative Vessels in Diabetic Retinopathy
Brief Summary This study proposes to carefully examine the hypothesis that human inducible pluripotent stem cells (iPSCs) can be effectively employed as a future therapeutic option for individuals with diabetic retinopathy and macular ischemia. iPSCs will be generated from the peripheral blood cells of subjects with diabetes and age matched controls. The human iPSC cells will be used to generate mesoderm cells for injection into the vitreous cavity of diabetic rodents and primate eyes. The ability of mesoderm cells to generate endothelial cells and pericytes in areas of degenerated capillaries will be examined. The human iPSCs will also be used to generate hematopoietic CD34+CD45+ cells. The combination of CD34+CD45+ cells derived from iPSCs and iPSC derived mesoderm will be examined in combination for their potentially beneficial effect to enhance the vessel formation.
Detailed Description

Vascular complications due to diabetes mellitus (DM) are the result of sustained vascular injury with insufficient vascular repair. In chronic diabetes, vascular reparative mechanism can be lost resulting in development of microvascular complications (MVC), such as diabetic retinopathy (DR). We assessed the reparative function of progenitor cells that circulate in the peripheral blood of diabetic individuals and found that the vascular wall-derived progenitor cells, endothelial colony forming cells (ECFCs), were depleted in diabetics with MVC. Bone marrow-derived progenitor cells, CD45+CD34+ were dysfunctional in diabetics with MVC. We found that human inducible pluripotent stem cells (hiPSCs)-derived ECFCs displayed the ability to form functional and durable blood vessels in vivo and conferred therapeutic revascularization by connecting with and remaining integrated with host rodent vessels long term. We characterized a mesoderm subset (SSEA5-KNA+ cells) generated from hiPSCs that gives rise to ECFCs. Finally, we used hiPSCs to generate CD34+CD45+ cells and tested the impact of co-administration of these cells with ECFCs within the vitreous. The addition of CD34+CD45+ cells with ECFCs resulted in the enhanced survival, function and reparative ability of the ECFCs. This beneficial effect was mediated by reducing retinal oxidative stress and inflammation.

These novel and paradigm shifting findings led us to hypothesize: the hiPSC-derived-mesoderm subset (SSEA5-KNA+) can be utilized for long term revascularization of vasodegenerative capillaries and their reparative action can be further enhanced by coinjection of CD34+CD45+ cells that provide anti-oxidant and anti-inflammatory effects.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Inducible pluripotent stem cells will be generated and cryopreserved.
Sampling Method Non-Probability Sample
Study Population Patients who have retinal abnormalities other than diabetic retinopathy will be excluded. Patients who have history of malignant disease or hematologic disorder. We will record medications that the patient is taking at the time of biopsy. Baseline characteristics will also be recorded, including age, lipid parameters, body mass index, blood pressure, smoking history, antioxidant intake and use of nutritional supplements.
Condition
  • Diabetes Complications
  • Diabetic Retinopathy
Intervention Biological: Generation of inducible pluripotent stem cells
Generation of inducible pluripotent stem cells from peripheral blood cells.
Study Groups/Cohorts
  • nondiabetics
    Any man or woman between the ages of 21- 98 years of age will be eligible to participate. To participate in the study as a study subject we will require: a) the subject must be a healthy control and b) the subject be willing and have the ability to cooperate with the eye exam and blood draw.
    Intervention: Biological: Generation of inducible pluripotent stem cells
  • Diabetic
    Any man or woman between the ages of 21- 98 years of age will be eligible to participate. To participate in the study as a study subject we will require: a) carry the diagnosis of diabetes and b) the subject be willing and have the ability to cooperate with the eye exam and blood draw.
    Intervention: Biological: Generation of inducible pluripotent stem cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: January 11, 2018)
20
Original Estimated Enrollment Same as current
Estimated Study Completion Date January 31, 2021
Estimated Primary Completion Date January 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Any man or woman between the ages of 21- 98 years of age will be eligible to participate. To participate in the study as a study subject we will require: a) the subject must either carry the diagnosis of diabetes or be a healthy aged control and b) the patient be willing and have the ability to cooperate with the eye exam and skin punch biopsy protocol.

Exclusion Criteria:

  • We will apply the following exclusion criteria: a) evidence of ongoing acute or chronic infection (HIV, Hepatitis B or C, tuberculosis); b) ongoing malignancy; c) cerebral vascular accident or cerebral vascular procedure; d) current pregnancy; e) history of organ transplantation; f) presence of a graft (to avoid any effect of the graft on inflammatory parameters; and g) patients with anemia. Subjects with AMD, glaucoma, uveitis, known hereditary degenerations or other significant ocular complications other than diabetic retinopathy will be excluded.
Sex/Gender
Sexes Eligible for Study: All
Ages 21 Years to 98 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Jennifer Moorer 205 325 8674 jmoorer@uabmc.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03403699
Other Study ID Numbers 300000173
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Maria Grant, University of Alabama at Birmingham
Study Sponsor University of Alabama at Birmingham
Collaborators Not Provided
Investigators
Principal Investigator: Maria B Grant, MD 1954
PRS Account University of Alabama at Birmingham
Verification Date February 2019