Centella Asiatica Selected Triterpenes (CAST) for Diabetic Neuropathy

Study Overview
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Brief Summary
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The purpose of this protocol is to investigate the safety, tolerability and effectiveness of CAST as a treatment for diabetic neuropathy. The primary outcome measure will be Total Neuropathic Symptom Score. Secondary outcomes will be neurological disability score, nerve conduction measurements and quantitative sensory testing. Statistical analyses will compare changes from baseline for CAST- and placebo-treated groups at both time points, compare effects of CAST at 6 and 12 months and, if numbers permit, compare doses.

Detailed Description
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This study is a clinical trial investigating the effect of an herbal supplement called CAST on diabetic neuropathy. CAST is an herb commonly used in traditional Indian medicine. In this tradition, it is used to increase memory, treat wounds and sores, skin diseases, and neurological conditions such as epilepsy. The herb has had growing popularity in the US; parts are sold as the dietary supplement gotu kola and used to improve blood circulation and help heal wounds. Unlike many other herbs, CAST has been extensively researched for many of the above conditions. The compounds found in CAST make it a very promising potential treatment for diabetic neuropathy because of its effect on blood circulation and growth of nerves. Subjects will receive informed consent. They will then be screened for eligibility before entering the study. A medical history will be taken and subjects will have a neurological exam and vital signs taken. Subjects will have their blood drawn and will also give a urine sample for routine testing. Subjects will have an electrocardiogram (ECG) to check their heart. If a subject is a woman who is at risk of getting pregnant, she will have a urine pregnancy test. If the subject is eligible for participation in the study, they will return for a total of nine additional study visits over the course of a year. Subjects will be randomly assigned to either receive the active supplement (CAST) or a placebo. A placebo is a pill that tastes, looks, and smells like the study drug but has no real medicine (or supplement) in it. Subjects have a 50% chance of receiving the active supplement. Neither the subject nor the study staff will know who receives the active supplement or the placebo. At visits 2, 7 and 10, subjects will get a comprehensive assessment of their neuropathy symptoms. This will include a Neurological Disability Score assessment, a nerve conduction study and a Quantitative Sensory Test. Subjects enrolled in the study will begin taking their study pills at the beginning of week 1 of the study. During the first 12 weeks, subjects will be asked to increase their dose by one pill every four weeks. Therefore, they will increase the number of CAST or placebo pills from 60mg twice daily to 60mg four times daily, or the highest dose that does not cause side effects. Dr. Lou will monitor subjects for side effects of the study supplement. At each study visit, blood and urine samples will be taken for safety analysis, including liver and kidney function, and glucose control, and an ECG will be done to monitor heart activity. Subjects will be contacted by the study coordinator via phone call once per week during the first three months of the study. During the remainder of the study, they will be called once each month that they are not scheduled for an appointment. Treatment will conclude after one year.

Official Title
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Centella Asiatica Triterpene Extract for Diabetic Neuropathy -- a Pilot Study

Conditions
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Diabetic Neuropathy

Intervention / Treatment
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* Drug: Centella asiatica selected triterpenes (CAST)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type II diabetes that is being treated with diet, oral antidiabetic agents and/or insulin stable glycemic control over the last 3 months evidence of symptomatic symmetrical distal neuropathy total symptom score of 4 or more stable HbA1c level of less than 8.5 over last three months Exclusion Criteria: Smokers Asymmetrical neuropathy of the trunk and proximal lower limbs Presence of foot ulcers Peripheral vascular disease (non-palpable foot pulses, intermittent claudication) Myopathy Causes of neuropathy other than diabetes Participation in a study of any investigational drug for diabetic neuropathy within 3 months of the study Use of any other product containing CA in the last 3 months Starting to use antioxidants or Vitamin B within 1 month before the study Severe concomitant diseases including neurological disease Pregnancy, lactation or being of child-bearing age without birth control HBA1c level higher than 8.5 Use of any experimental drugs in the three months prior to start of the study Use of anti-coagulant therapy (heparin or coumarin based drugs) A QTc of more than 500 ms at baseline ECG Uncontrollable hypertension, defined as diastolic pressure greater than 110, and systolic pressure greater than 160

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo CAST | Drug: Centella asiatica selected triterpenes (CAST)<br>* Drug provided to subjects in 60 mg capsules. Dose escalation phase: subjects take 2 capsules/day for weeks 1-4, 3 capsules/day for weeks 4-8 and 4 capsules/day weeks 8-12. Subjects remain on highest tolerated dose from week 12 to 52.<br>* Other names: Gotu Kola;|
| Active Comparator: Centella asiatica selected triterpenes<br>Active CAST | Other: Placebo<br>* Placebo provided to subjects in 60 mg color-matched capsules. Dose escalation phase: subjects take 2 capsules/day for weeks 1-4, 3 capsules/day for weeks 4-8 and 4 capsules/day weeks 8-12. Subjects remain on highest tolerated dose from week 12 to 52.<br>* Other names: Sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Symptom Score |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nerve Conduction Study |  | one year | 
| Neurological Disability Test |  | one year | 
| Quantitative Sensory Test |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAST, Centella asiatica, Diabetes, Diabetic neuropathy