Additional identifiers
EudraCT number
2008-008342-20
ClinicalTrials.gov number
Protocol/serial number
Sponsor ID: RAA08-015; EudraCT number: 2008-008342-20
Study information
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
Acronym
DOWNSLIT
Study hypothesis
That brain myo-inositol levels in non-demented Down's syndrome individuals can be reduced by a 4-week trial of lithium carbonate at therapeutic doses.
Ethics approval
South East Research Ethics Committee, 23/02/2009, ref: 09/H1102/3
Study design
Single-centre randomised single-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Down's syndrome
Intervention
Lithium carbonate (Camcolit®), 250 mg 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.
Intervention type
Drug
Phase
Not Applicable
Drug names
Lithium carbonate (Camcolit®)
Primary outcome measures
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 measures
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
Overall trial start date
01/06/2009
Overall trial end date
31/12/2011
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
34
Participant 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
Recruitment start date
01/06/2009
Recruitment end date
31/12/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Professor of Psychiatry and Brain Maturation
London
SE5 8AF
United Kingdom
Sponsor information
Organisation
King's College London (UK)
Sponsor details
c/o Professor Peter McGuffin
Dean and Head of School
Institute of Psychiatry
PO Box 001
De Crespigny Park
London
SE5 8AF
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Baily Thomas Charitable Fund (UK) (ref: 2215/1)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary