Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes
Słowa kluczowe
Abstrakcyjny
Opis
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.
Daktyle
| Ostatnia weryfikacja: | 08/31/2016 |
| Pierwsze przesłane: | 04/22/2009 |
| Szacowana liczba przesłanych rejestracji: | 04/22/2009 |
| Wysłany pierwszy: | 04/23/2009 |
| Ostatnia aktualizacja przesłana: | 09/19/2016 |
| Ostatnia opublikowana aktualizacja: | 10/25/2016 |
| Data pierwszego przesłania wyników: | 12/16/2015 |
| Data pierwszego przesłania wyników kontroli jakości: | 08/07/2016 |
| Data opublikowania pierwszych wyników: | 08/09/2016 |
| Rzeczywista data rozpoczęcia badania: | 04/30/2009 |
| Szacowana data zakończenia podstawowej działalności: | 06/30/2012 |
| Szacowana data zakończenia badania: | 06/30/2012 |
Stan lub choroba
Interwencja / leczenie
Drug: Idebenone 900 mg/day
Drug: Idebenone 2250 mg/day
Other: placebo
Faza
Grupy ramion
| Ramię | Interwencja / leczenie |
|---|---|
| Experimental: Idebenone 900 mg/day Idebenone 900 mg/day | Drug: Idebenone 900 mg/day 900 mg/day for 1 month |
| Experimental: Idebenone 2250 mg/day Idebenone 2250 mg/day | Drug: Idebenone 2250 mg/day 2250 mg/day for 1 month |
| Placebo Comparator: placebo Placebo | Other: placebo Placebo - No idebenone |
Kryteria kwalifikacji
| Wiek kwalifikujący się do nauki | 8 Years Do 8 Years |
| Płeć kwalifikująca się do nauki | All |
| Przyjmuje zdrowych wolontariuszy | tak |
| Kryteria | Inclusion Criteria: - 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) Exclusion Criteria: - 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 - 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 |
Wynik
Podstawowe miary wyników
1. Mean Change in Cerebral Lactate Concentration (as Measured by Magnetic Resonance Spectroscopy) [Up to 4 weeks from baseline]
Miary wyników wtórnych
1. Mean Change in Venous Lactate Concentration [Up to 4 weeks from baseline]
2. Mean Change in Score on the Fatigue Severity Scale (FSS) [Baseline and Week 4]
