Docosahexaenoic Acid (DHA) Replacement for Treatment in Spinocerebellar Ataxia 38 (SCA38DHA)
|ClinicalTrials.gov Identifier: NCT03109626|
Recruitment Status : Active, not recruiting
First Posted : April 12, 2017
Last Update Posted : May 24, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|SCA38||Dietary Supplement: DHA||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||double-blind randomised placebo-controlled phase, followed by an open-label phase|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Translating Molecular Pathology Into a Therapeutic Strategy in SCA38, a Newly Identified Form of Spinocerebellar Ataxia|
|Actual Study Start Date :||June 17, 2015|
|Actual Primary Completion Date :||September 17, 2015|
|Estimated Study Completion Date :||August 30, 2018|
Active Comparator: DHA administration
DHA 600 mg/day will be administered for 16 weeks to 5 patients in double blind
Dietary Supplement: DHA
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.
Dietary Supplement: DHA
- Change from Baseline SARA score at 16 weeks and 40 weeks [ Time Frame: baseline, 16 weeks, 40 weeks ]improvement of ataxia by SARA scores
- Change from Baseline ICARS score at 16 weeks and 40 weeks [ Time Frame: baseline, 16 weeks, 40 weeks ]improvement of ataxia by ICARS scores
- Brain FDG-PET [ Time Frame: baseline, 16 weeks, 40 weeks ]improvement of cerebellar hypometabolism
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03109626
|AO Spedali Civili|
|Brescia, BS, Italy, 25100|
|Principal Investigator:||Barbara Borroni, MD||AO Spedali Civili|