- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03109626
Docosahexaenoic Acid (DHA) Replacement for Treatment in Spinocerebellar Ataxia 38 (SCA38DHA)
Translating Molecular Pathology Into a Therapeutic Strategy in SCA38, a Newly Identified Form of Spinocerebellar Ataxia
The project will study a therapeutic approach in Spinocerebellar Ataxia (SCA38) by DHA replacement. SCA38 is caused by missense mutations in the ELOVL5 (Elongation of very long chain fatty acids protein 5) gene.
Background/Rationale: ELOVL5 is a microsomal fatty acid elongase gene required for the synthesis of arachidonic acid and DHA. In brain, it shows a peculiar high expression in cerebellar Purkinje cells.
The ELOVL5 products, such as DHA, are decreased in SCA38 patients serum and DHA administered as a dietary supplement has been shown to improve SARA scores, to ameliorate quality of life, and to increase brain cerebellar hypometabolism (FDG-PET) in two SCA38 patients.
Experimental Plan: The investigators will perform a randomized placebo-controlled trial by DHA supplementation on ten SCA38 patients, followed by an open-label phase.
Expected results: DHA supplementation should be able to improve symptoms in SCA38 and to improve cerebellar hypometabolism in these patients.
Study Overview
Detailed Description
Spinocerebellar ataxias (SCAs) include over thirty different subtypes of central nervous system diseases that affect approximately 1 in 30,000 persons. The investigators have identified the causative gene for SCA38, a novel rare form of cerebellar ataxia. Estimated frequency of the disease is below 1% of SCAs. The disease gene encodes an enzyme involved in omega-3 fatty acid biosynthesis, whose products are reduced in SCA38 patients' serum.
The investigators reasoned that the administration of specific omega-3 fatty acids could ameliorate the disease symptoms in SCA38 patients. Indeed, preliminary data obtained in a pilot trial on two patients, now in their 8th-month therapy, are remarkable, with an improvement of disease symptoms and quality of life, without any adverse effect.
The investigators will perform a clinical trial to prove this therapeutic strategy of SCA38. The investigators will evaluate clinical SARA scores, ICARS scores, brain PET images, and plasma metabolic pattern in ten SCA38 patients.
The trial will consist of two phases: 1) a randomized double-blind placebo/treatment (600 mg DHA/day) from T0 (baseline observation) to T1 (evaluation at four-month). Patients who will meet the study eligibility criteria will be randomized to receive the drug or the placebo (ratio 1:1). A second open-label phase on all patients from T2 (6 months) to T5 (30 months) will be performed with repeated measures of the medication group (n=10).
Patients will complete a personal diary during the whole treatment and a quality of life questionnaire at each visit. The primary outcome will be the clinical improvement, whilst secondary outcome will be considered the improvement of brain metabolism by PET-FDG.
At each time point, clinical evaluation (video-record of SARA/ICARS scores) will be performed. Videos will be randomized and evaluated blindly by two independently clinicians.
At T0, T1, T2, T5, patients will undergo brain PET-FDG scan. PET-FDG scans will be performed by the same scanner at the University of Brescia.
This project will provide helpful data on possible replacement treatment in this novel form of cerebellar degeneration.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
BS
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Brescia, BS, Italy, 25100
- AO Spedali Civili
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Mutations p.Gly230Val in ELOVL5 gene
- Clinical symptoms of ataxia
Exclusion Criteria:
- Use of fish oil or DHA dietary supplement within 30 days prior the enrollment in the present trial
- Evidence of poorly controlled diabetes (defined as hemoglobin A1c > 8% in patients with diabetes)
- Average alcohol consumption of more than one drink or equivalent (>12 g) per day or more than two drinks on any 1 day over the 30 days prior to screening.
- Serum creatinine level 2.0 mg/dL or greater or currently on dialysis
- Evidence of drug abuse within 6 months prior to entering the study or during the screening period
- Reported poor compliance to drug assumption
- Bedridden patients (SARA score >23)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: DHA administration
DHA 600 mg/day will be administered for 16 weeks to 5 patients in double blind
|
|
Placebo Comparator: placebo administration
placebo will be made with the same colour and taste, in softgel as DHA, and will be administered for 16 weeks to 5 patients in double blind.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change from Baseline SARA score at 16 weeks and 40 weeks
Time Frame: baseline, 16 weeks, 40 weeks
|
improvement of ataxia by SARA scores
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baseline, 16 weeks, 40 weeks
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Change from Baseline ICARS score at 16 weeks and 40 weeks
Time Frame: baseline, 16 weeks, 40 weeks
|
improvement of ataxia by ICARS scores
|
baseline, 16 weeks, 40 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Brain FDG-PET
Time Frame: baseline, 16 weeks, 40 weeks
|
improvement of cerebellar hypometabolism
|
baseline, 16 weeks, 40 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Barbara Borroni, MD, AO Spedali Civili
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Genetic Diseases, Inborn
- Neurodegenerative Diseases
- Dyskinesias
- Spinal Cord Diseases
- Heredodegenerative Disorders, Nervous System
- Cerebellar Diseases
- Cerebellar Ataxia
- Ataxia
- Spinocerebellar Ataxias
- Spinocerebellar Degenerations
Other Study ID Numbers
- CE NP1821
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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