Genetically determined brain abnormalities in Down's syndrome - towards a treatment: Down's syndrome Lithium Trial

• Register: ISRCTN
• Last refreshed on: 12 February 2013
• Main ID: ISRCTN03784241
• Date of registration: 19/08/2009
• Primary sponsor: King's College London (UK)
• Public title: Genetically determined brain abnormalities in Down's syndrome - towards a treatment: Down's syndrome Lithium Trial DOWNSLIT
• Scientific title: Genetically determined brain abnormalities in Down's syndrome - towards a treatment: A randomised, single-blind, placebo controlled trial of lithium carbonate in Down's syndrome
• Date of first enrolment: Jun 1 2009
• Target sample size: 34
• Recruitment status: Completed/Not recruiting
• URL: http://isrctn.org/ISRCTN03784241
• Study type: Interventional
• Study design: Single centre randomised single-blind placebo controlled trial

Countries of recruitment

United Kingdom

Contacts

• Name: Declan Murphy

Key inclusion & exclusion criteria

Inclusion criteria: 1. Individuals with Down's syndrome
2. Over the age of 18 years, either sex
3. Able to provide informed consent for themselves or have a representative to provide proxy consent on their behalf if they lack capacity
4. Able to communicate with the investigator and to comply with requirements of the study
5. Has carer support
Exclusion criteria: 1. Individuals with contraindications to lithium treatment
2. Individuals with contraindications to undergoing a magnetic resonance scan
3. Non-compliance with taking of the tablets between baseline and the final assessment
4. Treatment with lithium within the last 6 months
5. Evidence of dementia
6. Evidence of renal, thyroid or cardiac disease that would contraindicate taking lithium
7. Pregnancy

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Down's syndrome

Intervention(s)

Lithium carbonate (Camcolit®), 250mg oral tablets versus placebo.

Titration phase: dose adjusted to achieve therapeutic plasma level of 0.4 - 1.0 mmol/l
Maintenance phase: twice daily dosing for 4 weeks on therapeutic lithium carbonate dose
Titration Phase: Dose adjusted to achieve therapeutic plasma level of 0.4-1.0mmol/L
Maintenance Phase: Twice daily dosing for 4 weeks on therapeutic lithium carbonate dose

Total duration of treatment is around 8 weeks; follow-up will be as appropriate if patients have any side-efects on Lithium, otherwise patient involvement ends when they come off the medication. Likewise for placebo group.

Primary Outcome(s)

Brain myo-inositol concentrations (dorsolateral prefrontal cortex [DLPFC] and hippocampus) measured by 1H magnetic resonance spectroscopy (MRS) at baseline and after 4 weeks maintenance lithium treatment at therapeutic dose.

Secondary Outcome(s)

1. Blood biomarkers which have been implicated in the development of Alzheimer's Disease:
1.1. Isolation of genomic DNA for studies of genotype in relation to response including the Tau haplotype, Intron 7 repeat of APP, and ApoE4
1.2. Abeta1-40, Abeta1-42 base fragments and other amyloid species
1.3. Markers of amyloid oxidative stress e.g. isoprostane and other members
1.4. Markers of systemic inflammation e.g. IL-6, TNF-alpha and other inflammatory markers
1.5. Other markers of APP processing e.g. BACE
2. Cognitive measures:
2.1. British Picture Vocabulary Scale (BPVS) at baseline
2.2. Cambridge Examination for mental disorders of the elderly revised (CAMDEX-R) section on Cognitive Examination (CAMCOG) after 4 weeks maintenance lithium treatment at therapeutic dose

Secondary ID(s)

Sponsor ID: RAA08-015; EUDRACT Number: 2008-008342-20

Source(s) of Monetary Support

Baily Thomas Charitable Fund (UK) (ref: 2215/1)

Secondary Sponsor(s)

N/A