Lithium and Acetate for Canavan Disease

Canavan Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00657748
• Other study ID #: P070803
• Status: Withdrawn
• Phase: Phase 2
• First received: April 9, 2008
• Last updated: April 20, 2015
• Start date: September 2009
• Est. completion date: January 2011

Study information

• Verified date: April 2015
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 15 Years

Eligibility

Inclusion Criteria:

• Clinical and biochemical diagnosis of Canavan disease

Exclusion Criteria:

• Renal disease

• Thyroid disease

• Cardiac disease

• Impossibility to perform brain MRI

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aspartoacylase
• Canavan Disease
• Deficiency Disease
• Deficiency Diseases
• Infantile
• Leukodystrophy, Spongiform

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	European Leukodystrophy Association

References & Publications (4)

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. — View Citation

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. — View Citation

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 Ac — View Citation

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 O — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	-Improvement of epilepsy (number of seizures)		10 months	Yes
Secondary	-Decrease in NAA and increase in acetate contents in fluids (CSF, plasma, urine).		10 months	Yes

External Links

•   ELA (European Leukodystrophy Association)