Lithium and Acetate for Canavan Disease

This study has been withdrawn prior to enrollment.
European Leukodystrophy Association
Information provided by:
Assistance Publique - Hôpitaux de Paris Identifier:
First received: April 9, 2008
Last updated: April 20, 2015
Last verified: April 2015
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.

Condition Intervention Phase
Canavan Disease
Deficiency Disease
Leukodystrophy, Spongiform
Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of the Tolerance and Efficiency of a Combined Oral Therapy With Lithium and GTA in Patients With Canavan Disease

Resource links provided by NLM:

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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. [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
  • -Improvement of epilepsy (number of seizures) [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
  • -Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine). [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: September 2009
Study Completion Date: January 2011
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Lithium Gluconate (drug) Glyceryl Triacetate GTA (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
Other Names:
  • Lithium Gluconate (drug)
  • Glyceryl Triacetate, GTA (drug)

Detailed Description:
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.

Ages Eligible for Study:   1 Year to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Clinical and biochemical diagnosis of Canavan disease

Exclusion Criteria:

  • Renal disease
  • Thyroid disease
  • Cardiac disease
  • Impossibility to perform brain MRI
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Please refer to this study by its identifier: NCT00657748

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
European Leukodystrophy Association
Principal Investigator: Patrick Aubourg, MD, PhD Assistance Publique - Hôpitaux de Paris
Principal Investigator: Caroline Sevin, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

Additional Information:
Responsible Party: Yannick VACHER, Department Clinical Research and Developpement Identifier: NCT00657748     History of Changes
Other Study ID Numbers: P070803
Study First Received: April 9, 2008
Last Updated: April 20, 2015
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Canavan disease,
Glyceryl Triacetate

Additional relevant MeSH terms:
Canavan Disease
Deficiency Diseases
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Demyelinating Diseases
Genetic Diseases, Inborn
Hereditary Central Nervous System Demyelinating Diseases
Heredodegenerative Disorders, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurodegenerative Diseases
Nutrition Disorders
Lithium Carbonate
Anti-Infective Agents
Antidepressive Agents
Antifungal Agents
Antimanic Agents
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions processed this record on November 24, 2015