Chinese Medicine WT for Spinocerebellar Ataxia Type 3

• ClinicalTrials.gov Identifier: NCT05038306
• Recruitment Status: Completed
• First Posted: September 9, 2021
• Last Update Posted: January 31, 2023
• Sponsor: Changhua Christian Hospital
• Information provided by (Responsible Party): Chiu Chung Min, Changhua Christian Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Ataxia, Spinocerebellar; Insulin-Like Growth Factor I; Medicine, Chinese Traditional	Drug: Chinese medicine WT	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Chinese Medicine WT for Elevating IGF-1 of Patients With Spinocerebellar Ataxia Type 3 - Pilot Study
• Actual Study Start Date: May 31, 2021
• Actual Primary Completion Date: September 26, 2022
• Actual Study Completion Date: September 26, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Chinese Medicine	Drug: Chinese medicine WT; 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.
Placebo Comparator: Placebo	Drug: Chinese medicine WT; 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change from baseline in scale for the assessment and rating of ataxia(SARA) at week 12, or from week 16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   scores of SARA are from 0 to 40, with higher scores means worse outcome
2. Change from baseline in Modified Fatigue Impact Scale (MFIS) at week 12, or from week 16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   scores of MFIS are from 0 to 84, with higher scores means worse outcome
3. Change from baseline in Epworth Sleepiness Scale (ESS) at week 12, or from week16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   scores of ESS are from 0 to 24, with higher scores means worse outcome
4. Change from baseline in Hand-grip strength test (HST) at week 12, or from week16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   HST is appropriate to observe the change for a period instead of the absolute value
5. Change from baseline in mitochondria DNA (mtDNA) at week 12, or from week16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   mitochondrial DNA HST is appropriate to observe the change for a period instead of the absolute value
6. Change from baseline in 8_OHdG at week 12, or from week16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   8_OHdG is appropriate to observe the change for a period instead of the absolute value
7. Change from baseline in △Ct at week 12, or from week16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   △Ct is appropriate to observe the change for a period instead of the absolute value
8. Change from baseline in serum metabolites at week 12, or from week 16 to week 28 [ Time Frame: baseline and 12 weeks, or 16 weeks and 28 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Taiwan

Changhua Christian Hospital

Changhua, Taiwan, 500

Sponsors and Collaborators

Changhua Christian Hospital

More Information

• Responsible Party: Chiu Chung Min, Adjunct Physician, Changhua Christian Hospital
• ClinicalTrials.gov Identifier: NCT05038306
• Other Study ID Numbers: 200703
• First Posted: September 9, 2021
• Last Update Posted: January 31, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease; Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn