Docosahexaenoic Acid (DHA) Replacement for Treatment in Spinocerebellar Ataxia 38

NCT03109626 | Completed DMC

• 1 other identifier: CE NP1821
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

SCA38

Keywords

DHA, replacement, treatment, brain PET-FDG, ataxia

Outcome Measures

Primary Outcomes (2)

• Change from Baseline SARA score at 16 weeks and 40 weeks

  improvement of ataxia by SARA scores

  baseline, 16 weeks, 40 weeks

• Change from Baseline ICARS score at 16 weeks and 40 weeks

  improvement of ataxia by ICARS scores

  baseline, 16 weeks, 40 weeks

Secondary Outcomes (1)

• Brain FDG-PET

  baseline, 16 weeks, 40 weeks

Study Arms (2)

DHA administration

ACTIVE COMPARATOR

DHA 600 mg/day will be administered for 16 weeks to 5 patients in double blind

Dietary Supplement: DHA

placebo administration

PLACEBO COMPARATOR

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

Interventions

DHA DIETARY_SUPPLEMENT

DHA administration; placebo administration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Mutations p.Gly230Val in ELOVL5 gene
• Clinical symptoms of ataxia

You may not qualify if:

• 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)

Sponsors & Collaborators

• Barbara Borroni: lead

Study Sites (1)

AO Spedali Civili

Brescia, BS, 25100, Italy

Location

Related Publications (1)

• Di Gregorio E, Borroni B, Giorgio E, Lacerenza D, Ferrero M, Lo Buono N, Ragusa N, Mancini C, Gaussen M, Calcia A, Mitro N, Hoxha E, Mura I, Coviello DA, Moon YA, Tesson C, Vaula G, Couarch P, Orsi L, Duregon E, Papotti MG, Deleuze JF, Imbert J, Costanzi C, Padovani A, Giunti P, Maillet-Vioud M, Durr A, Brice A, Tempia F, Funaro A, Boccone L, Caruso D, Stevanin G, Brusco A. ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum Genet. 2014 Aug 7;95(2):209-17. doi: 10.1016/j.ajhg.2014.07.001. Epub 2014 Jul 24.

  PMID: 25065913 BACKGROUND

MeSH Terms

Conditions

Ataxia

Condition Hierarchy (Ancestors)

Dyskinesias; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Barbara Borroni, MD

  AO Spedali Civili

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associated Professor of Neurology, MD

Model Details: double-blind randomised placebo-controlled phase, followed by an open-label phase

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 12, 2017
• Study Start: June 17, 2015
• Primary Completion: September 17, 2015
• Study Completion: June 25, 2018
• Last Updated: December 31, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share

Locations

IT (1)