Ex Vivo Immunotherapy for Hyperglycemia in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Diabetes mellitus type 2 is a long-term metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency and hyperglycemia. Our hypotheses is that liver would be the primary organ responsible for the metabolic disorder because of some unknown defects, where sugar would not be efficiently converted to glycogen and fat, leading to hyperglycemia. The constant hyperglycemia would keep pressure on beta-cells in the pancreas to eventually exhaust their ability to produce and secret sufficient amount of insulin, exacerbating the disease. The Immunotherapy would enhance the liver functions and correct the abnormal sugar metabolism. In addition, the ex vivo activated cells produce and secret growth factors which would help endothelial cells of blood vessels to reproduce and grow, resulting in reduced arteriosclerosis.

Detailed Description
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We plan to recruit 20 patients with type 2 diabetes mellitus who suffer hyperglycemia with or without medication. The patients will come to our hospitals for the treatment. A small amount of peripheral blood will be drawn and processed and cultured in our laboratory. The cultured cells (autologous) will be infused intravenously back to patients. Levels of plasma hemoglobin A1c (HbA1c) and other metabolic parameters before and after the therapy will be compared. The therapy is planned to take four weeks for each patient.

Official Title
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Pilot Study of a Cell-Based Therapy for Treatment of Hyperglycemia in Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus, Hyperglycemia

Intervention / Treatment
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* Drug: ex vivo Activated Immune Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Patients diagnosed with type 2 diabetes mellitus. 2. 25 years of age or older. Both sexes. 3. HbA1c ≧6.5% for more than 6 months with or without medication. 4. Capability of providing informed consent. Exclusion Criteria: 1. History of malignancy. 2. Patients with active infections. 3. Seropositivity for HIV infection. 4. History of myocardial infarction or unstable angina in the previous 3 months. 5. Pregnancy or nursing.

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ex vivo activated immune cells<br>Up to 20 patients diagnosed with type 2 diabetes mellitus and hyperglycemia will be enrolled and assigned to a single treatment group. Patients will give a small amount of peripheral blood and the blood will be processed and cultured in our laboratory. The ex vivo activated autologous blood cells will be infused intravenously back to patients. The treatment will be done twice a week for consecutive 4 weeks. The metabolic parameters of patients before and after the therapy will be compared to determine if the therapy is safe and effective. | Drug: ex vivo Activated Immune Cells<br>* The patients who take medication before the enrollment will be required to reduce at least half the amount of the medication before the treatment. The reduction of the medication will continue during and after the therapy until the levels of plasma hemoglobin A1c (HbA1c) increase to equal or above the levels of the baseline measured before the treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Hemoglobin A1c (HbA1c) at up to 27 weeks. |  | Point 1: The week (week 1) before the first cell infusion assessed as the baseline; Point 2: The week (week 6) after the last cell infusion; Point 3 and after: every 4 weeks up to 27 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline Lipid Profile at up to 27 weeks. | Lipid profile includes cholesterol, triglycerides, HDL cholesterol and LDL cholesterol. | Point 1: The week (week 1) before the first cell infusion assessed as the baseline; Point 2: The week (week 6) after the last cell infusion; Point 3 and after: every 4 weeks up to 27 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus Type 2, Hyperglycemia, Immunotherapy, Autologous