Chinese Medicine WT for Spinocerebellar Ataxia Type 3

Study Overview
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Brief Summary
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Spinocerebellar ataxia type 3 (SCA3) is one of autosomal dominant hereditary ataxias. Standing imbalance, unsteady gait, dysmetria, fatigue, and depression would occur gradually. There are no effective treatment or palliative methods for patients in the present days. However, low-dose growth hormone, or its downstream product, insulin-like growth factor I (IGF-1), may deter the progress of SCA3 in transgenic mice. The main bioactive constituent among the Chinese medicine WT possesses neuroprotective function against glutamate-induced toxicity, which is one major pathology of SCA3. It promotes neurogenesis, and increases the protein expression of IGF-1 in ischemic brains of rats. Thus, we designed a randomized, double-blind trial for patients with SCA3, if WT is a possible neuroprotective medicine. All the subjects will be recruited from Changhua Christian Hospital. Diagnosis is confirmed by gene test and magnetic resonance image by a neurologist. They will be assigned in random and double blind, prescribed with 3 grams concentrated powder of WT or placebo, twice a day, for 12 weeks. After the washout period of 4 weeks, there will be a crossover of placebo or WT for another 12 weeks. After that, another 4-week rest will be followed by the end of trial. Check items in five check points include: 1. Blood examination (serum IGF-1, Neurofilament light chain, mitochondria copy number, 8_OHdG, delta-Ct), 2.Neurological exam (Scale for the Assessment and Rating of Ataxia), 3. Questionnaires (Modified Fatigue Impact Scale, Epworth Sleepiness Scale), 4. Handgrip strength test (which is correlated to IGF-1 value in elderly), and 5. serum metabolites, . All the data will be disclosed after the end of trial. Paired-T test or Wilcoxon Ranked Sign Test will be operated in SPSS.

Official Title
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Chinese Medicine WT for Elevating IGF-1 of Patients With Spinocerebellar Ataxia Type 3 - Pilot Study

Conditions
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Ataxia, Spinocerebellar, Insulin-Like Growth Factor I, Medicine, Chinese Traditional

Intervention / Treatment
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* Drug: Chinese medicine WT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed as Spinocerebellar Ataxia type 3 Exclusion Criteria: 1. using other Chinese medicine or herbal medicine 2. allergic to Chinese medicine or herbal medicine 3. pregnancy or breast feeding 4. with other major diseases, such as cancer, stroke, heart failure, or renal failure

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chinese Medicine<br> | Drug: Chinese medicine WT<br>* The Chinese medicine WT is thought to be neurotrophic, and its major constituent may benefit IGF-1 in animal studies, or certain healthy human group. WT is safe in clinical use in Asia.<br>|
| Placebo Comparator: Placebo<br> | Drug: Chinese medicine WT<br>* The Chinese medicine WT is thought to be neurotrophic, and its major constituent may benefit IGF-1 in animal studies, or certain healthy human group. WT is safe in clinical use in Asia.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Insulin-like Growth Factor 1 at week 12, or from week 16 to week 28 | Insulin-like growth factor I is appropriate to observe the change for a period instead of the absolute value. | baseline and 12 weeks, or 16 weeks and 28 weeks, 32 weeks | 
| Change from baseline in Neurofilament light Chain at week 12, or from week 16 to week 28 | Neurofilament light Chain is appropriate to observe the change for a period instead of the absolute value | baseline and 12 weeks, or 16 weeks and 28 weeks, 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in scale for the assessment and rating of ataxia(SARA) at week 12, or from week 16 to week 28 | scores of SARA are from 0 to 40, with higher scores means worse outcome | baseline and 12 weeks, or 16 weeks and 28 weeks | 
| Change from baseline in Modified Fatigue Impact Scale (MFIS) at week 12, or from week 16 to week 28 | scores of MFIS are from 0 to 84, with higher scores means worse outcome | baseline and 12 weeks, or 16 weeks and 28 weeks | 
| Change from baseline in Epworth Sleepiness Scale (ESS) at week 12, or from week16 to week 28 | scores of ESS are from 0 to 24, with higher scores means worse outcome | baseline and 12 weeks, or 16 weeks and 28 weeks | 
| Change from baseline in Hand-grip strength test (HST) at week 12, or from week16 to week 28 | HST is appropriate to observe the change for a period instead of the absolute value | baseline and 12 weeks, or 16 weeks and 28 weeks | 
| Change from baseline in mitochondria DNA (mtDNA) at week 12, or from week16 to week 28 | mitochondrial DNA HST is appropriate to observe the change for a period instead of the absolute value | baseline and 12 weeks, or 16 weeks and 28 weeks | 
| Change from baseline in 8_OHdG at week 12, or from week16 to week 28 | 8_OHdG is appropriate to observe the change for a period instead of the absolute value | baseline and 12 weeks, or 16 weeks and 28 weeks | 
| Change from baseline in △Ct at week 12, or from week16 to week 28 | △Ct is appropriate to observe the change for a period instead of the absolute value | baseline and 12 weeks, or 16 weeks and 28 weeks | 
| Change from baseline in serum metabolites at week 12, or from week 16 to week 28 | serum metabolites is appropriate to observe the change for a period instead of the absolute value. Till now, there was no sufficient data about the metabolites of Chinese WT, so we would like to measure the difference of metabolites before and after taking the Chinese medicine WT. | baseline and 12 weeks, or 16 weeks and 28 weeks |