Friedreich AtaxiaPhase 1NCT00078481
Phase 1 Trial of Idebenone to Treat Patients With Friedreich's Ataxia
A Phase 1 study testing Idebenone in people with Friedreich Ataxia, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will determine the highest amount of idebenone that can be taken without harmful side effects in children, teenagers, and adults with Friedreich's ataxia, a progressive degenerative disease that affects several body systems. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Friedreich Ataxia
- What is being tested?
- Idebenone
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2004to Apr 2006
- Phase
- Phase 1
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of FRDA with confirmed FRDA mutations.
- Age greater than or equal to five years.
- No exposure to idebenone or coenzyme Q(10) for a period of at least one week before onset of the medication phase of the study.
- Written, informed consent (and assent, if applicable).
Who cannot join
- History of hypersensitivity reaction to idebenone or coenzyme Q(10).
- Pregnant or lactating women. All women of child-bearing potential must have negative serum pregnancy prior to the medication phase of the study. If a minor has a positive pregnancy test, we will inform her but not inform her parents unless we are asked to by the minor.
- Lactose intolerant individuals (because of the lactose content in the tablet ingredients).
- Age less than five years old.
- Platelet count, lymphocyte count or hemoglobin below the lower limit of normal.
- Alkaline phosphatase, SGOT, or SGPT greater than 1.5 x the upper limit of normal. Bilirubin greater than 1.2 g/dl.
- Creatinine greater than 1.5 x the upper limit of normal.
- Clinically significant medical disease that, in the judgment of the investigators, would expose the patient to undue risk of harm or prevent the patient from completing the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: Phase 1B Clinical Trial to Establish the Safety and Tolerability of a Multiple-Dose Regimen of Idebenone Administered to Patients With Friedreich's Ataxia
This study will determine the highest amount of idebenone that can be taken without harmful side effects in children, teenagers, and adults with Friedreich's ataxia, a progressive degenerative disease that affects several body systems. Studies in France and Canada showed that patients with Friedreich's ataxia who took idebenone had a decrease in the size of their left ventricle (main pumping chamber of the heart), which is often enlarged in this disease. It is possible that idebenone may also prevent the progression of nervous system degeneration in Friedreich's ataxia.
Patients 5 years of age and older with Friedreich's ataxia may be eligible for this study. Candidates are screened with a blood test and review of their medical records, including genetic studies.
Read more
Participants undergo the following procedures during a 6-day hospital admission to the NIH Clinical Center:
- Placement of an intravenous catheter (plastic tube inserted into a vein) for collecting blood samples after drug administration
- Blood and urine tests
- Heart examination, including electrocardiogram (EKG), to assess heart function and size.
- Idebenone therapy: Patients take three tablets a day (at 7 AM, 1 PM and 7 PM) on days 2, 3 and 4 of hospitalization. Blood samples are collected through the IV tube at 0.5, 1, 2, 4, and 6 hours after the first dose on day 2, then at 1 hour after the first and third doses every day, and then at 1, 2, 4, 8, 12, 24, 36, and 48 hours after the last dose on day 4 to determine how the body uses and eliminates the drug.
- Monitoring for drug side effects: Patients have frequent checks of vital signs (blood pressure, pulse, temperature, breathing rate) and a brief physical examination to check for drug side effects from the start of drug therapy on day 2 until at least 43 hours after the last dose on day 4.
Patients who experience no difficulties are discharged from the hospital after the sixth day with a 1-month supply of medication to take 3 times a day at home. They are contacted by phone every 2 weeks while taking the medication to check side effects. Blood tests are also done every 2 weeks to check for any abnormalities.
Read the detailed description
Background: Friedreich's ataxia (FRDA) is a progressive, autosomal recessive, multisystem degenerative disease for which there is currently no effective treatment. Recent studies have demonstrated that lipid-soluble antioxidants lead to a modest reversal of cardiomyopathy in patients with FRDA. It is possible that antioxidants may also prevent the progression of neurodegeneration.
Objective: This will be a phase 1B, unblinded trial examining the toxicity and tolerability of the antioxidant idebenone given as a multiple-dose regimen for a short inpatient course and then long term to patients with FRDA.
Study Population: We aim to enroll 15 patients divided evenly among three age cohorts: children (ages 5-11), adolescents (ages 12-17), and adults (age greater than or equal to 18).
Design: Our primary objective is to examine the tolerability of idebenone given at a dose of 60 mg/kg/day for 72 hours (total of 9 doses) in an inpatient setting (NIH Clinical Center). This dose is below the maximum dose examined (75 mg/kg/day) that was well tolerated with no dose-limiting toxicity (DLT) in our phase 1A (protocol# 01-N-0167) study. The 72 hour course represents 5.5 half-lives of the drug based upon previous studies of the drug in healthy human subjects and our phase 1A data, thereby allowing the serum concentration of the drug to reach steady-state levels. This multiple dose regimen will allow us to examine accumulation of the drug and to examine tolerability of the drug at a steady-state concentration. The patients will then be followed by inpatient monitoring for an additional 43 hours, representing 3.3 half-lives, to allow relatively complete elimination of the drug. If no adverse events are noted during the inpatient phase of the trial, patients will resume taking the drug on an outpatient basis for 1 month to determine long-term tolerability and compliance. Outpatients will be followed through phone interviews by the NIH research team along with routine blood work every 2 weeks. Our secondary objective is to document the pharmacokinetics, specifically the apparent distribution volume (Vd), elimination half-life (t1/2), elimination clearance (CLE), and steady-state concentrations (CSS) of idebenone during the inpatient phase of the study.
Outcome Parameters: Outcomes in this phase I trial are types and frequency of adverse events, if any, and compliance with the dosing regimen. Our secondary endpoint is pharmacokinetics of this dosing regimen.
Future Directions: We hope to follow these phase I studies with a multicenter, double-blinded, placebo-controlled phase III trial using an ataxia scale developed for FRDA as the primary endpoint.
- Conditions
- Friedreich Ataxia
- Being tested
- Idebenone
- Keywords
- Neurodegeneration, Anti-Oxidant, Neuropathy, Hereditary, Spinocerebellar, Friedreich Ataxia, FRDA
- Medical subject headings
- Friedreich Ataxia, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IdebenoneDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2004 (estimated)
- Study startFeb 2004
- Study completionApr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Friedreich AtaxiaStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Enrolment
- 16 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00078481
- Sponsor's protocol ID
- 040129
- Other IDs
- 04-N-0129
- Status last verified
- Apr 2006
- First submitted
- 27 Feb 2004
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Artuch R, Aracil A, Mas A, Colome C, Rissech M, Monros E, Pineda M. Friedreich's ataxia: idebenone treatment in early stage patients. Neuropediatrics. 2002 Aug;33(4):190-3. doi: 10.1055/s-2002-34494.
PubMed 12368988Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science. 1997 Jun 13;276(5319):1709-12. doi: 10.1126/science.276.5319.1709.
PubMed 9180083Beal MF. Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci. 2000 Jul;23(7):298-304. doi: 10.1016/s0166-2236(00)01584-8.
PubMed 10856939Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP. Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia. Arch Neurol. 2007 Jun;64(6):803-8. doi: 10.1001/archneur.64.6.803.
PubMed 17562928
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1B Clinical Trial to Establish the Safety and Tolerability of a Multiple-Dose Regimen of Idebenone Administered to Patients With Friedreich's Ataxia
- ClinicalTrials.gov ID
- NCT00078481
- Acronym / sponsor ID
- 040129
- Conditions
- Friedreich Ataxia
- Keywords
- Neurodegeneration, Anti-Oxidant, Neuropathy, Hereditary, Spinocerebellar, Friedreich Ataxia, FRDA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Feb 2004
- Study completion
- Apr 2006
- First posted
- 1 Mar 2004 (estimated)
- 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.
This study will determine the highest amount of idebenone that can be taken without harmful side effects in children, teenagers, and adults with Friedreich's ataxia, a progressive degenerative disease that affects several body systems. Studies in France and Canada showed that patients with Friedreich's ataxia who took idebenone had a decrease in the size of their left ventricle (main pumping chamber of the heart), which is often enlarged in this disease. It is possible that idebenone may also prevent the progression of nervous system degeneration in Friedreich's ataxia.
Patients 5 years of age and older with Friedreich's ataxia may be eligible for this study. Candidates are screened with a blood test and review of their medical records, including genetic studies.
Participants undergo the following procedures during a 6-day hospital admission to the NIH Clinical Center:
- Placement of an intravenous catheter (plastic tube inserted into a vein) for collecting blood samples after drug administration
- Blood and urine tests
- Heart examination, including electrocardiogram (EKG), to assess heart function and size.
- Idebenone therapy: Patients take three tablets a day (at 7 AM, 1 PM and 7 PM) on days 2, 3 and 4 of hospitalization. Blood samples are collected through the IV tube at 0.5, 1, 2, 4, and 6 hours after the first dose on day 2, then at 1 hour after the first and third doses every day, and then at 1, 2, 4, 8, 12, 24, 36, and 48 hours after the last dose on day 4 to determine how the body uses and eliminates the drug.
- Monitoring for drug side effects: Patients have frequent checks of vital signs (blood pressure, pulse, temperature, breathing rate) and a brief physical examination to check for drug side effects from the start of drug therapy on day 2 until at least 43 hours after the last dose on day 4.
Patients who experience no difficulties are discharged from the hospital after the sixth day with a 1-month supply of medication to take 3 times a day at home. They are contacted by phone every 2 weeks while taking the medication to check side effects. Blood tests are also done every 2 weeks to check for any abnormalities.
Detailed description
Background: Friedreich's ataxia (FRDA) is a progressive, autosomal recessive, multisystem degenerative disease for which there is currently no effective treatment. Recent studies have demonstrated that lipid-soluble antioxidants lead to a modest reversal of cardiomyopathy in patients with FRDA. It is possible that antioxidants may also prevent the progression of neurodegeneration.
Objective: This will be a phase 1B, unblinded trial examining the toxicity and tolerability of the antioxidant idebenone given as a multiple-dose regimen for a short inpatient course and then long term to patients with FRDA.
Study Population: We aim to enroll 15 patients divided evenly among three age cohorts: children (ages 5-11), adolescents (ages 12-17), and adults (age greater than or equal to 18).
Design: Our primary objective is to examine the tolerability of idebenone given at a dose of 60 mg/kg/day for 72 hours (total of 9 doses) in an inpatient setting (NIH Clinical Center). This dose is below the maximum dose examined (75 mg/kg/day) that was well tolerated with no dose-limiting toxicity (DLT) in our phase 1A (protocol# 01-N-0167) study. The 72 hour course represents 5.5 half-lives of the drug based upon previous studies of the drug in healthy human subjects and our phase 1A data, thereby allowing the serum concentration of the drug to reach steady-state levels. This multiple dose regimen will allow us to examine accumulation of the drug and to examine tolerability of the drug at a steady-state concentration. The patients will then be followed by inpatient monitoring for an additional 43 hours, representing 3.3 half-lives, to allow relatively complete elimination of the drug. If no adverse events are noted during the inpatient phase of the trial, patients will resume taking the drug on an outpatient basis for 1 month to determine long-term tolerability and compliance. Outpatients will be followed through phone interviews by the NIH research team along with routine blood work every 2 weeks. Our secondary objective is to document the pharmacokinetics, specifically the apparent distribution volume (Vd), elimination half-life (t1/2), elimination clearance (CLE), and steady-state concentrations (CSS) of idebenone during the inpatient phase of the study.
Outcome Parameters: Outcomes in this phase I trial are types and frequency of adverse events, if any, and compliance with the dosing regimen. Our secondary endpoint is pharmacokinetics of this dosing regimen.
Future Directions: We hope to follow these phase I studies with a multicenter, double-blinded, placebo-controlled phase III trial using an ataxia scale developed for FRDA as the primary endpoint.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of FRDA with confirmed FRDA mutations.
- Age greater than or equal to five years.
- No exposure to idebenone or coenzyme Q(10) for a period of at least one week before onset of the medication phase of the study.
- Written, informed consent (and assent, if applicable).
Key exclusion criteria (8 listed)
- History of hypersensitivity reaction to idebenone or coenzyme Q(10).
- Pregnant or lactating women. All women of child-bearing potential must have negative serum pregnancy prior to the medication phase of the study. If a minor has a positive pregnancy test, we will inform her but not inform her parents unless we are asked to by the minor.
- Lactose intolerant individuals (because of the lactose content in the tablet ingredients).
- Age less than five years old.
- Platelet count, lymphocyte count or hemoglobin below the lower limit of normal.
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 |
|---|---|---|
| Idebenone | Drug | – |
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 12368988Artuch R, Aracil A, Mas A, Colome C, Rissech M, Monros E, Pineda M. Friedreich's ataxia: idebenone treatment in early stage patients. Neuropediatrics. 2002 Aug;33(4):190-3. doi: 10.1055/s-2002-34494.
- Background: PubMed 9180083Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science. 1997 Jun 13;276(5319):1709-12. doi: 10.1126/science.276.5319.1709.
- Background: PubMed 10856939Beal MF. Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci. 2000 Jul;23(7):298-304. doi: 10.1016/s0166-2236(00)01584-8.
- Derived from this study: PubMed 17562928Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP. Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia. Arch Neurol. 2007 Jun;64(6):803-8. doi: 10.1001/archneur.64.6.803.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Idebenone in people with Friedreich Ataxia, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 4 inclusion and 8 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 4 Mar 2008. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00078481, which also lists 4 linked publications.
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 4 Mar 2008.