Lithium and Acetate for Canavan Disease

Brief Title

Lithium and Acetate for Canavan Disease

Official Title

Evaluation of the Tolerance and Efficiency of a Combined Oral Therapy With Lithium and GTA in Patients With Canavan Disease

Brief Summary

      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.

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.

Study Phase

Phase 2

Study Type


Primary Outcome

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.

Secondary Outcome

 Secondary outcomes will be assessed at 10 months (end of the treatment): -Improvement of neuromotor performances (GMFM and Mullen scales), spasticity, and neurological severity


Canavan Disease


Lithium Gluconate (drug) Glyceryl Triacetate GTA (drug)

Study Arms / Comparison Groups



* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

September 2009

Completion Date

January 2011

Primary Completion Date

September 2010

Eligibility Criteria

        Inclusion Criteria:

          -  Clinical and biochemical diagnosis of Canavan disease

        Exclusion Criteria:

          -  Renal disease

          -  Thyroid disease

          -  Cardiac disease

          -  Impossibility to perform brain MRI




1 Year - 15 Years

Accepts Healthy Volunteers



Patrick Aubourg, MD, PhD, , 

Administrative Informations



Organization ID


Study Sponsor

Assistance Publique - Hôpitaux de Paris


 European Leukodystrophy Association

Study Sponsor

Patrick Aubourg, MD, PhD, Principal Investigator, Assistance Publique - Hôpitaux de Paris

Verification Date

April 2015