MELAS SyndromePhase 2MELASNCT00887562
Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
A Phase 2 study testing Idebenone in people with MELAS Syndrome, run by Michio Hirano at 1 site in United States.
Trial summary
The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy. Read more about this study
- Who is it for?
- Ages 8 to 65 years
- Conditions the study is for
- MELAS Syndrome
- What is being tested?
- Idebenone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- May 2009to Jul 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 8 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss)
- Cerebral lactate level equal to or greater than 5.0 i.u. at baseline
- Patients at least 8 and < 65 years of age at baseline
- Patients with a body weight > 37 kg/82 lbs at baseline
- Stable co-medication/vitamins/supplements within 1 month prior to baseline
- Patients who in the opinion of the investigator are able to comply with the requirements of the study, including swallowing the study medication
- Negative urine pregnancy test at screening and baseline (female patients of childbearing potential)
Who cannot join
- Contraindication to MRS (e.g. metal implant, claustrophobia)
- Stroke like event within 2 months prior to baseline
- Treatment with idebenone at any dose, or coenzyme Q10 at doses above 100mg/d within 1 month prior to baseline
- Inadequate contraception use
- Pregnancy and/or breast-feeding
- Clinically significant abnormalities of clinical hematology or biochemistry including, but not limited to, elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or creatinine
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- Current abuse of drugs or alcohol
- Participation in a trial of another investigational drug within the last month
- Other factor that, in the investigator's opinion, excludes the patient from entering the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Medical Center
New York, New York, 10032
About this study
Official title: A Phase IIa Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes
The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy.
Read the detailed description
MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes), a progressive and often devastating multisystem disorder, is most commonly associated with mitochondrial Deoxyribonucleic acid (mtDNA) point mutation at nucleotide 3243. Seizures, cognitive deterioration, and neurobehavioral abnormalities are frequent features of this disease which typically shortens life expectancy. Idebenone, an ATP production modulator and antioxidant, improves neurological function in Friedreich's ataxia, a disease also associated with mitochondrial dysfunction.
Given that there is no effective treatment for MELAS, the investigators propose a Phase II proof of concept trial of idebenone to study its preliminary efficacy in patients with MELAS and the A3243G mtDNA mutation, and to study its safety and tolerability in this patient group.
The investigators propose to evaluate 21 patients with the A3243G mitochondrial DNA mutation and MELAS (defined by a history of either seizures or stroke). Patients will receive idebenone (900 mg/day or 2250 mg/day) or matching placebo for one month. The primary outcome measure is cerebral lactate levels measured by Magnetic Resonance Spectroscopy (MRS), a biomarker associated with disease worsening. This study will help the investigators to determine if there is sufficient signal to proceed to efficacy studies. Also it will provide additional information on the safety and tolerability of two different doses of idebenone in MELAS.
- Conditions
- MELAS Syndrome
- Being tested
- Idebenone, Placebo
- Medical subject headings
- MELAS Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IdebenoneDrug
Also called active drug
900 mg/day for 1 month
IdebenoneDrug
Also called active drug
2250 mg/day for 1 month
PlaceboOther
Also called No active drug
Placebo - No idebenone
| Study group | Role | What they receive |
|---|---|---|
| Idebenone 900 mg/day | Experimental | Idebenone 900 mg/day Receives: Drug: Idebenone |
| Idebenone 2250 mg/day | Experimental | Idebenone 2250 mg/day Receives: Drug: Idebenone |
| placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)
To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on cerebral lactate concentration as measured by magnetic resonance spectroscopy (MRS)
Measured: Up to 4 weeks from baseline
Secondary outcomes (2)
Mean Change in Venous Lactate Concentration
To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on venous lactate concentration
Measured: Up to 4 weeks from baseline
Mean Change in Score on the Fatigue Severity Scale (FSS)
To assess changes following 1 month treatment with 2 different doses of idebenone with that of placebo in fatigue as assessed by the Fatigue Severity Scale (FSS).
Scale score minimum is 9 (least fatigue) and maximum is 63 (maximum fatigue). Scores of 36 or less indicate possibility that patient may not be suffering from fatigue, while scores 36 and over suggest suffering from fatigue
Measured: Baseline and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MELAS SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michio Hirano
- Sponsor type
- University, hospital or other
- Collaborators
- Santhera Pharmaceuticals
- Responsible party
- Sponsor-investigator, Michio Hirano, Columbia University
- Investigators
- Michio Hirano, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00887562
- Sponsor's protocol ID
- AAAC9240
- Other IDs
- SNT-II-007
- Acronym
- MELAS
- Status last verified
- Sep 2016
- First submitted
- 23 Apr 2009
- Last updated
- 26 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIa Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes
- ClinicalTrials.gov ID
- NCT00887562
- Acronym / sponsor ID
- MELAS / AAAC9240
- Conditions
- MELAS Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Michio HiranoUniversity, hospital or other
- Collaborators
- Santhera Pharmaceuticals
- Study start
- May 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 24 Apr 2009 (estimated)
- Results
- Posted 10 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the efficacy of two (2) different doses of idebenone with that of a placebo over a one month period on cerebral lactate concentration as measured by magnetic resonance spectroscopy.
Detailed description
MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes), a progressive and often devastating multisystem disorder, is most commonly associated with mitochondrial Deoxyribonucleic acid (mtDNA) point mutation at nucleotide 3243. Seizures, cognitive deterioration, and neurobehavioral abnormalities are frequent features of this disease which typically shortens life expectancy. Idebenone, an ATP production modulator and antioxidant, improves neurological function in Friedreich's ataxia, a disease also associated with mitochondrial dysfunction.
Given that there is no effective treatment for MELAS, the investigators propose a Phase II proof of concept trial of idebenone to study its preliminary efficacy in patients with MELAS and the A3243G mtDNA mutation, and to study its safety and tolerability in this patient group.
The investigators propose to evaluate 21 patients with the A3243G mitochondrial DNA mutation and MELAS (defined by a history of either seizures or stroke). Patients will receive idebenone (900 mg/day or 2250 mg/day) or matching placebo for one month. The primary outcome measure is cerebral lactate levels measured by Magnetic Resonance Spectroscopy (MRS), a biomarker associated with disease worsening. This study will help the investigators to determine if there is sufficient signal to proceed to efficacy studies. Also it will provide additional information on the safety and tolerability of two different doses of idebenone in MELAS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Idebenone 900 mg/day | Experimental | Drug: IdebenoneIdebenone 900 mg/day |
| Idebenone 2250 mg/day | Experimental | Drug: IdebenoneIdebenone 2250 mg/day |
| placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 8 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Diagnosis of MELAS with confirmed A3243G mtDNA mutation, or evidence of central nervous system involvement (cognitive problems, migraines, memory loss)
- Cerebral lactate level equal to or greater than 5.0 i.u. at baseline
- Patients at least 8 and < 65 years of age at baseline
- Patients with a body weight > 37 kg/82 lbs at baseline
- Stable co-medication/vitamins/supplements within 1 month prior to baseline
Key exclusion criteria (9 listed)
- Contraindication to MRS (e.g. metal implant, claustrophobia)
- Stroke like event within 2 months prior to baseline
- Treatment with idebenone at any dose, or coenzyme Q10 at doses above 100mg/d within 1 month prior to baseline
- Inadequate contraception use
- Pregnancy and/or breast-feeding
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 |
|---|---|---|
| IdebenoneAlso: active drug900 mg/day for 1 month | Drug | Idebenone 900 mg/day |
| IdebenoneAlso: active drug2250 mg/day for 1 month | Drug | Idebenone 2250 mg/day |
| PlaceboAlso: No active drugPlacebo - No idebenone | Other | placebo |
Primary outcome
Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy)
Time frame: Up to 4 weeks from baseline
To compare the efficacy of 1 month treatment with 2 different doses of idebenone with that of placebo on cerebral lactate concentration as measured by magnetic resonance spectroscopy (MRS)
2 secondary outcomes
Mean Change in Venous Lactate Concentration
Time frame: Up to 4 weeks from baseline
Mean Change in Score on the Fatigue Severity Scale (FSS)
Time frame: Baseline and Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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MELAS or m.3243 A>G Mitochondrial DNA Mutation Carrier
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.
Michio Hirano, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Idebenone in people with MELAS Syndrome, run by Michio Hirano at 1 site in United States.
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 7 inclusion and 9 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 26 Oct 2016. 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy) (time frame: Up to 4 weeks from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Oct 2016.