SCA38SCA38DHANCT03109626
Docosahexaenoic Acid (DHA) Replacement for Treatment in Spinocerebellar Ataxia 38
A study testing DHA in people with SCA38, run by Barbara Borroni at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SCA38
- What is being tested?
- DHA
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- 17 Jun 2015to 25 Jun 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Mutations p.Gly230Val in ELOVL5 gene
- Clinical symptoms of ataxia
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- SCA38
- Being tested
- DHA
- Keywords
- DHA, replacement, treatment, brain PET-FDG, ataxia
- Medical subject headings
- Ataxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DHADietary supplement
| Study group | Role | What they receive |
|---|---|---|
| DHA administration | Active comparator | DHA 600 mg/day will be administered for 16 weeks to 5 patients in double blind Receives: 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. Receives: Dietary Supplement: DHA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline SARA score at 16 weeks and 40 weeks
improvement of ataxia by SARA scores
Measured: baseline, 16 weeks, 40 weeks
Change from Baseline ICARS score at 16 weeks and 40 weeks
improvement of ataxia by ICARS scores
Measured: baseline, 16 weeks, 40 weeks
Secondary outcomes (1)
Brain FDG-PET
improvement of cerebellar hypometabolism
Measured: baseline, 16 weeks, 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2017
- Study start17 Jun 2015
- Primary completion17 Sep 2015
- Study completion25 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SCA38Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blind randomised placebo-controlled phase, followed by an open-label phase
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Barbara Borroni
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Barbara Borroni, MD, Principal investigator, AO Spedali Civili
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03109626
- Sponsor's protocol ID
- CE NP1821
- Acronym
- SCA38DHA
- Status last verified
- Dec 2018
- First submitted
- 31 Mar 2017
- Last updated
- 31 Dec 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: to share data after study publication
Publications
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.
PubMed 25065913
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Translating Molecular Pathology Into a Therapeutic Strategy in SCA38, a Newly Identified Form of Spinocerebellar Ataxia
- ClinicalTrials.gov ID
- NCT03109626
- Acronym / sponsor ID
- SCA38DHA / CE NP1821
- Conditions
- SCA38
- Keywords
- DHA, replacement, treatment, brain PET-FDG, ataxia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Barbara BorroniUniversity, hospital or other
- Study start
- 17 Jun 2015 (actual)
- Primary completion
- 17 Sep 2015 (actual)
- Study completion
- 25 Jun 2018 (actual)
- First posted
- 12 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind randomised placebo-controlled phase, followed by an open-label phase
| Arm | Type | Receives |
|---|---|---|
| DHA administration | Active comparator | Dietary Supplement: DHADHA 600 mg/day will be administered for 16 weeks to 5 patients in double blind |
| placebo administration | Placebo comparator | Dietary Supplement: DHAplacebo 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Mutations p.Gly230Val in ELOVL5 gene
- Clinical symptoms of ataxia
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DHA | Dietary supplement | DHA administration, placebo administration |
Primary outcome
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
1 secondary outcome
Brain FDG-PET
Time frame: baseline, 16 weeks, 40 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2018.
- Background: PubMed 25065913Di 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.
- Individual participant dataSharing planned: Yes. to share data after study publication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara Borroni, MD principal investigator
AO Spedali Civili
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DHA in people with SCA38, run by Barbara Borroni at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline SARA score at 16 weeks and 40 weeks (time frame: baseline, 16 weeks, 40 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03109626, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Dec 2018.