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
EudraCT/CTIS number 2008-008342-20
Secondary identifying numbers Sponsor ID: RAA08-015; EudraCT number: 2008-008342-20
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

Study designSingle-centre randomised single-blind placebo-controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleGenetically 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 acronymDOWNSLIT
Study objectivesThat 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) studiedDown's syndrome
InterventionLithium 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Lithium carbonate (Camcolit®)
Primary outcome measureBrain 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 measures1. 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 study start date01/06/2009
Completion date31/12/2011

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants34
Total final enrolment19
Key inclusion criteria1. 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 criteria1. 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 enrolment01/06/2009
Date of final enrolment31/12/2011

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Professor of Psychiatry and Brain Maturation
London
SE5 8AF
United Kingdom

Sponsor information

King's College London (UK)
University/education

c/o Professor Peter McGuffin
Dean and Head of School
Institute of Psychiatry
PO Box 001
De Crespigny Park
London
SE5 8AF
England
United Kingdom

Website http://www.iop.kcl.ac.uk/
ROR logo "ROR" https://ror.org/0220mzb33

Funders

Funder type

Charity

Baily Thomas Charitable Fund (UK) (ref: 2215/1)
Private sector organisation / Trusts, charities, foundations (both public and private)
Alternative name(s)
The Baily Thomas Charitable Fund
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot 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

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.