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

ISRCTN	ISRCTN03784241
DOI	https://doi.org/10.1186/ISRCTN03784241
Clinical Trials Information System (CTIS)	2008-008342-20
Protocol serial number	Sponsor ID: RAA08-015; EudraCT number: 2008-008342-20
Sponsor	King's College London (UK)
Funder	Baily Thomas Charitable Fund (UK) (ref: 2215/1)

Submission date: 28/05/2009
Registration date: 19/08/2009
Last edited: 20/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Other

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Declan Murphy
Scientific

Professor of Psychiatry and Brain Maturation
Institute of Psychiatry
Section of Brain Maturation, PO50
De Crespigny Park
London
SE5 8AF
United Kingdom

Study information

Primary study design	Interventional
Study design	Single-centre randomised single-blind placebo-controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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
Study acronym	DOWNSLIT
Study objectives	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(s)	South East Research Ethics Committee, 23/02/2009, ref: 09/H1102/3
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Lithium carbonate (Camcolit®)
Primary outcome measure(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.
Key secondary outcome measure(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
Completion date	31/12/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	34
Total final enrolment	19
Key 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
Key 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
Date of first enrolment	01/06/2009
Date of final enrolment	31/12/2011

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Professor of Psychiatry and Brain Maturation

London
SE5 8AF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			20/05/2019	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

20/05/2019: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrollment was added.
12/04/2017: No publications found in PubMed, verifying study status with principal investigator.