The Peripheral Mobilized Mononuclear Cell-based Therapy in Patient With Diabetic Neuropathy

Study Overview
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Brief Summary
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To investigate the efficacy and safety of autologous peripheral blood stem cell based therapy in patients with diabetic painful neuropathy.

Detailed Description
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Diabetic painful neuropathy a prevalent, disabling disorder. Currently, the only effective treatments are glucose control and pain management. Diabetic neuropathy is characterized by reduction of vascularity in peripheral nerves and deficiency in neurotrophic and angiogenic factors. Recent studies have shown that bone marrow (BM)-derived stem or progenitor cells have favorable effects on the repair of cardiovascular diseases. Since these BM-derived stem or progenitor cells contain various angiogenic and neurotrophic factors, these cells have been attempted for treating experimental diabetic neuropathy, and turned out to be effective for reversing various manifestations of experimental diabetic neuropathy. However, stem-cell therapy was not proven in human study. Therefore, we will investigate the efficacy and safety of autologous peripheral blood stem cell injection in diabetic neuropathy.

Official Title
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The Efficacy and Safety of Peripheral Mobilized Mononuclear Cell-based Therapy in Patients With Diabetic Painful Neuropathy

Conditions
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Diabetic Neuropathy

Intervention / Treatment
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* Biological: Normal saline
* Biological: stem-cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: symptomatic diabetic neuropathy moderate pain more than 3 months Michigan Neuropathy Screening Instrument (MNSI) >3 3/day mean pain scale > NRS 4 Body weight >50 kg systolic blood pressure: 90-150 mmHg, Diastolic blood pressure <100 mmHg, Body temperature <37.5℃, Pulse rate: 50-100/min Exclusion Criteria: other cause of neuropathy symptomatic peripheral vessel disease skin lesion or arthritis central neuronal disease drug addiction or abuse Aspartate aminotransferase or Alanine aminotransferase >1.5 times than upper normal limit range Creatinine clearance rate <60ml/min or dialysis Myocardial infarction, unstable angina or heart failure diagnosed in 3 months psychologic disorder pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: control<br>The operator inject normal saline(control) to thirty site of the other side leg of active comparator. The volume of one site injection is 0.5 ml. The depth of needle injection would be 1.5cm. | Biological: Normal saline<br>* Normal saline is injected in one leg of patient.<br>|
| Active Comparator: stem cell (mononuclear cell)<br>The stem cell (mononuclear cell) is injected to thirty site of one side leg in operating room after general anesthesia. The volume of one site injection is 0.5 to 1.0 ml. The depth of needle injection would be 1.5cm. | Biological: stem-cell<br>* Granulocyte colony-stimulating factor (G-CSF) is injected into subcutaneous for three days prior to the blood collection (D-3 to D-1). Peripheral mononuclear stem-cell is collected by Cobe spectra apheresis system in D-day. The stem-cell (mononuclear cell) is injected into the muscle in the other side leg of patient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pain for a week after the procedure | The pain scale was calculate by Numeric rating scale (NRS). We observe a change in NRS pain scores during the follow-up period. | baseline, 4 week, 12 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The evaluation of changes in the specific neuro-sensory system | The following tests was evaluated during the follow-up period. The pain intensity was evaluated by short-form McGill Pain Questionnaire and by sleep disturbance pain score. The quantitative change of sensory nerve was evaluated by quantitative sensory test (QST). We measure serum neuron-specific enolase (NSE), glucose, insulin and c-peptide. The amount of drug requirements will also assess at each follow-up period. | baseline, 4 week, 12 week |