Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| European Leukodystrophy Association | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The aim of this study is to determine whether oral supplementation with lithium and acetate may improve the biological and clinical prognosis in patients with Canavan Disease.
Canavan Disease is an autosomal recessive devastating demyelinating disease caused by a deficiency in Aspartoacylase (ASPA) enzyme. There is no available treatment. ASPA deficiency leads to:- the accumulation of high levels of N-acetylaspartate (NAA), involved in myelin degeneration and epilepsy;- the deficient synthesis of acetate in oligodendrocytes, that could impair CNS myelination.Lithium administration induces a decrease in NAA in the brain of the tremor rats (animal model for CD) and in one patient (JANSON, 2005). On the other hand, administration of acetate could improve myelination in Canavan patients.For this reason, we propose to combine both treatments: Lithium Gluconate and Glyceryl Triacetate (GTA). Eighteen patients, aged 1 to 15 years, will receive oral GTA or Lithium during 4 months, then both treatment in association during 6 months. Patients will be sequentially evaluated up to the end of the treatment and 2 months thereafter for:-tolerance of the therapy (careful monitoring of clinical and biological parameters).- efficacy of the therapy on clinical, biological and radiological parameters. Particularly, we will evaluate using MRI-spectroscopy and CSF samples the decrease in NAA and increase in acetate levels in the brain.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug) | Drug | Lithium 1.3 mEq/kg/day (three administrations a day)during the study GTA 500 mg/kg/day in four administrations a day during the study |
| Measure | Description | Time Frame |
|---|---|---|
| The primary outcome will be a decrease of the NAA peak (> 20%) or the appearance of an acetate peak at the end of the treatment (10 months), using spectroscopy-MRI. | 10 months |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity | 10 months | |
| -Improvement of epilepsy (number of seizures) | 10 months |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Patrick Aubourg, MD, PhD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Caroline Sevin, MD, PhD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16002461 | Result | Mathew R, Arun P, Madhavarao CN, Moffett JR, Namboodiri MA. Progress toward acetate supplementation therapy for Canavan disease: glyceryl triacetate administration increases acetate, but not N-acetylaspartate, levels in brain. J Pharmacol Exp Ther. 2005 Oct;315(1):297-303. doi: 10.1124/jpet.105.087536. Epub 2005 Jul 7. | |
| 15784740 | Result |
| Label | URL |
|---|---|
| ELA (European Leukodystrophy Association) | View source |
Not provided
| ID | Term |
|---|---|
| D017825 | Canavan Disease |
| D003677 | Deficiency Diseases |
| ID | Term |
|---|---|
| D020279 | Hereditary Central Nervous System Demyelinating Diseases |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C030691 | gluconic acid |
| D004364 | Pharmaceutical Preparations |
| D014215 | Triacetin |
| ID | Term |
|---|---|
| D014280 | Triglycerides |
| D005989 | Glycerides |
| D008055 | Lipids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| -Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine). | 10 months |
| Madhavarao CN, Arun P, Moffett JR, Szucs S, Surendran S, Matalon R, Garbern J, Hristova D, Johnson A, Jiang W, Namboodiri MA. Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease. Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5221-6. doi: 10.1073/pnas.0409184102. Epub 2005 Mar 22. |
| 16194720 | Result | Janson CG, Assadi M, Francis J, Bilaniuk L, Shera D, Leone P. Lithium citrate for Canavan disease. Pediatr Neurol. 2005 Oct;33(4):235-43. doi: 10.1016/j.pediatrneurol.2005.04.015. |
| 12064356 | Result | Baslow MH, Kitada K, Suckow RF, Hungund BL, Serikawa T. The effects of lithium chloride and other substances on levels of brain N-acetyl-L-aspartic acid in Canavan disease-like rats. Neurochem Res. 2002 May;27(5):403-6. doi: 10.1023/a:1015504031229. |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D056784 | Leukoencephalopathies |
| D003711 | Demyelinating Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |