Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00229632
Status:
COMPLETED
Last Update Posted:
2019-03-18
First Post:
2005-09-29
Brief Title:
Idebenone to Treat Friedreichs Ataxia
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Six Month Double-Blind Placebo-Controlled Phase 2 Clinical Trial to Determine the Safety and Efficacy of Idebenone Administered to Patients With Friedreichs Ataxia
Status:
COMPLETED
Status Verified Date:
2019-03-14
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will determine whether a drug called idebenone is safe and effective in reducing the level of oxidants that are believed to damage the nervous system and hearts in patients with Friedreichs ataxia Friedreichs ataxia is caused by an abnormality in the gene that makes a protein called frataxin which is necessary for the proper functioning of energy-producing parts of cells called mitrochondria In Friedreichs ataxia the mitochondria become overloaded with iron and high levels of harmful compounds called oxidants are formed These oxidants are believed to damage the cells of the nervous system and hearts of people with Friedreichs ataxia Idebenone is a man-made drug similar to a naturally occurring compound known as Coenzyme Q10 This study will test whether idebenone can alleviate some of the symptoms of Friedreichs ataxia and slow or halt the progression of the disease
Patients with genetically confirmed Friedreichs ataxia who are between 9 and 18 years of age weigh between 65 and 175 pounds and can walk 25 feet with or without an assistive device may be eligible for this study Candidates are screened with blood tests and a review of their medical records
Participants undergo the following tests and procedures
Medical interview and physical examination Tests include blood and urine tests an electrocardiogram or EKG recording of the electrical activity of the heart echocardiogram ultrasound test showing the pumping action of the heart thickness of the heart walls and any valve leakage and a detailed neurological examination including maneuvers such as copying a drawing and putting pegs in a board Patients parents are asked questions about how they feel their childs disease affects the childs quality of life
Magnetic resonance imaging MRI to examine the heart muscle and blood flow to the heart MRI uses a magnetic field and radio waves to produce images of body tissues and organs The patient lies on a table that is moved into the doughnut-shaped MRI scanner wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process A catheter plastic tube is placed in a vein in the childs arm so that a chemical called gadolinium can be injected during the MRI study Gadolinium brightens areas of the heart improving the ability to see the heart and blood flow
Physical medicine and rehabilitation evaluations to test the childs physical functioning These tests include gait evaluation measurements of the ability to exert and maintain a constant force assessment of visual-motor control and fine motor control aerobic exercise endurance testing and measurement of the ability of the childs heart and lungs to increase their effectiveness with exercise
Idebenoneplacebo treatment Patients are given a 6-month supply of either idebenone pills or placebo pills that look like the study drug but have no active ingredient to take three times a day Patients are seen by their primary care physician after 1 and 3 months on the study medication for a brief physical examination In addition they have blood and urine tests once a month while on medication to check for any abnormalities
6-month examination After 6 months on the study drug patients return to NIH to repeat all the tests listed above to determine the effects of idebenone treatment
Patients with genetically confirmed Friedreichs ataxia who are between 9 and 18 years of age weigh between 65 and 175 pounds and can walk 25 feet with or without an assistive device may be eligible for this study Candidates are screened with blood tests and a review of their medical records
Participants undergo the following tests and procedures
Medical interview and physical examination Tests include blood and urine tests an electrocardiogram or EKG recording of the electrical activity of the heart echocardiogram ultrasound test showing the pumping action of the heart thickness of the heart walls and any valve leakage and a detailed neurological examination including maneuvers such as copying a drawing and putting pegs in a board Patients parents are asked questions about how they feel their childs disease affects the childs quality of life
Magnetic resonance imaging MRI to examine the heart muscle and blood flow to the heart MRI uses a magnetic field and radio waves to produce images of body tissues and organs The patient lies on a table that is moved into the doughnut-shaped MRI scanner wearing earplugs to muffle loud knocking and thumping sounds that occur during the scanning process A catheter plastic tube is placed in a vein in the childs arm so that a chemical called gadolinium can be injected during the MRI study Gadolinium brightens areas of the heart improving the ability to see the heart and blood flow
Physical medicine and rehabilitation evaluations to test the childs physical functioning These tests include gait evaluation measurements of the ability to exert and maintain a constant force assessment of visual-motor control and fine motor control aerobic exercise endurance testing and measurement of the ability of the childs heart and lungs to increase their effectiveness with exercise
Idebenoneplacebo treatment Patients are given a 6-month supply of either idebenone pills or placebo pills that look like the study drug but have no active ingredient to take three times a day Patients are seen by their primary care physician after 1 and 3 months on the study medication for a brief physical examination In addition they have blood and urine tests once a month while on medication to check for any abnormalities
6-month examination After 6 months on the study drug patients return to NIH to repeat all the tests listed above to determine the effects of idebenone treatment
Detailed Description:
Background Friedreichs ataxia FA is a progressive autosomal recessive multisystem degenerative disease for which there is currently no effective treatment Recent studies have suggested that lipid-soluble antioxidants lead to a modest reversal of cardiomyopathy in patients with FA It is possible that antioxidants may also prevent the progression of neurodegeneration
Objective This will be a 6 month phase 2 double-blind placebo-controlled trial to assess the safety and efficacy of idebenone administered to adolescents and children with FA
Study Population We aim to enroll 48 subjects composed of children ages 9-11 and adolescents ages 12-17 with FA divided evenly among 4 treatment arms placebo low intermediate and high dose idebenone
Design Our primary objective is to examine the change in the level of oxidative stress by measuring the oxidative marker 8-hydroxy-2-deoxyguanosine from baseline and after 6 months of treatment with placebo or varying doses of idebenone Following informed consent and assent patients will undergo an initial medical history and physical followed by specific neurological functional and cardiac testing over a two-day outpatient visit Patients will provide blood and urine samples for safety laboratory and biochemical analysis Each patient will be randomized to one of 4 treatment arms and will be provided with a 6 month supply of study drug or placebo which will be administered three times a day Patients will have follow-up laboratory monitoring after 1 and 3 months and at the end of the study Additionally patients will also have an EKG vital signs including orthostatics and a physical examination performed after 1 and 3 months by their primary care physician Patients will return after 6 months for follow-up exam testing and laboratory monitoring over a two-day outpatient visit
Outcome Parameters The primary endpoint in this phase 2 trial is the change in the level of the oxidative stress marker 8-hydroxy-2-deoxyguanosine Secondary endpoints include types and frequency of adverse events if any compliance with the dosing regimen and measurements of the following International Cooperative Ataxia Rating Scale ICARS Friedreichs ataxia Rating Scale FARS force control gait analysis quantitative sensation testing fine motor control health related quality of life score SF-10 functional capacity aerobic capacity left ventricular wall mass noninvasive measures of systolic and diastolic ventricular function metabolic markers markers of mitochondrial DNA damage and gene expression profiling
Future Directions We hope that the results of this phase 2 study will assist us in developing a multi-center double-blinded placebo-controlled phase III trial
Objective This will be a 6 month phase 2 double-blind placebo-controlled trial to assess the safety and efficacy of idebenone administered to adolescents and children with FA
Study Population We aim to enroll 48 subjects composed of children ages 9-11 and adolescents ages 12-17 with FA divided evenly among 4 treatment arms placebo low intermediate and high dose idebenone
Design Our primary objective is to examine the change in the level of oxidative stress by measuring the oxidative marker 8-hydroxy-2-deoxyguanosine from baseline and after 6 months of treatment with placebo or varying doses of idebenone Following informed consent and assent patients will undergo an initial medical history and physical followed by specific neurological functional and cardiac testing over a two-day outpatient visit Patients will provide blood and urine samples for safety laboratory and biochemical analysis Each patient will be randomized to one of 4 treatment arms and will be provided with a 6 month supply of study drug or placebo which will be administered three times a day Patients will have follow-up laboratory monitoring after 1 and 3 months and at the end of the study Additionally patients will also have an EKG vital signs including orthostatics and a physical examination performed after 1 and 3 months by their primary care physician Patients will return after 6 months for follow-up exam testing and laboratory monitoring over a two-day outpatient visit
Outcome Parameters The primary endpoint in this phase 2 trial is the change in the level of the oxidative stress marker 8-hydroxy-2-deoxyguanosine Secondary endpoints include types and frequency of adverse events if any compliance with the dosing regimen and measurements of the following International Cooperative Ataxia Rating Scale ICARS Friedreichs ataxia Rating Scale FARS force control gait analysis quantitative sensation testing fine motor control health related quality of life score SF-10 functional capacity aerobic capacity left ventricular wall mass noninvasive measures of systolic and diastolic ventricular function metabolic markers markers of mitochondrial DNA damage and gene expression profiling
Future Directions We hope that the results of this phase 2 study will assist us in developing a multi-center double-blinded placebo-controlled phase III trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-N-0245 | None | None | None |