Contact information
Type
Scientific
Primary contact
Prof Harald Hampel
ORCID ID
Contact details
Discipline of Psychiatry
School of Medicine and Trinity College Institute of Neuroscience (TCIN)
Trinity College
University of Dublin
The Adelaide and Meath Hospital Incorporating The National Children's Hospital (AMiNCH)
Tallaght
Dublin
24
Ireland
+353 (0)1 896 3706
harald.hampel@tcd.ie
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
D0200C00001
Study information
Scientific title
Acronym
Study hypothesis
Ten-week treatment with lithium affects glycogen synthase kinase-3 (GSK-3) activity and cerebrospinal fluid (CSF) levels of phosphorylated tau (p-tau) in patients with mild Alzheimer's disease.
Ethics approval
Ethics approval received from:
1. Ethics Committee of the Medical Faculty of the Ludwig-Maximilians University of Munich (Ethikkommission der Medizinischen Fakultät der Ludwig-Maximilians Universität München) on the 10th September 2004 (ref: 208/04)
2. Ethics Commitee of the Ruprecht-Karl University of Heidelberg (Ethikkommission der Ruprecht-Karl-Universität Heidelberg) on the 12th November 2004 (ref: 366/2004)
3. Ethics Committee of the Ruprecht-Karl University of Heidelberg, Faculty for Clinical Medicine Mannheim on the 18th November 2004 (ref: 220/04)
4: Ethics Committee of Charité Berlin (Ethikkommission der Charité Berlin) on the 11th November 2004 (ref: EA4/036/04)
5: Ethics Committee of the University of Tübingen (Ethikkommission der Universität Tübingen) on the 12th October 2004 (ref: 341/2004G)
6. Ethics Committee of the Faculty for Medicine of the Technical University of Munich (Ethikkommission der Fakultät für Medizin der Technischen Universität München) on the 3rd November (ref: 1191/04)
Study design
Randomised, single-blind, placebo controlled, parallel-group multicentre study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Alzheimer's disease
Intervention
Following enrolment visit and baseline assessments, eligible patients were randomised to receive lithium sulphate (Lithionit®) or placebo (randomised 1:1), and entered into a titration phase of six weeks. During the titration phase, there were weekly visits to adjust the lithium dose to the target serum lithium concentration of 0.5 - 0.8 mmol/L. The starting dose of lithium sulphate, 42 mg (6 mmol Li+), was 1 + 1 tablets daily (one tablet in the morning and one tablet in the evening approximately 12 hours apart). Dosages were escalated at weekly intervals until the target serum lithium concentration of 0.5 - 0.8 mmol/L (measured 12 hours from last dose) was reached, with 4 + 4 tablets taken during the maintenance phase.
Total duration of treatment: 10 weeks
Follow-up: at baseline and end of treatment (10 weeks)
Intervention type
Drug
Phase
Not Specified
Drug names
Lithium
Primary outcome measures
The following were assessed at baseline and the end of treatment (10 weeks):
1. Change in GSK-3 activity in lymphocytes
2. Change in p-tau181 and p-tau231 in CSF
Secondary outcome measures
The following were assessed at baseline and the end of treatment (10 weeks):
1. Change in beta-amyloid (1-42) in CSF and blood
2. Change in tau in CSF
3. Change in cognitive function as measured by cognitive subscore of the Alzheimer's Disease Assessment Scale (ADAScog) and Neuropsychiatric Inventory (NPI)
4. To monitor safety and tolerability
Overall trial start date
22/11/2004
Overall trial end date
29/07/2005
Reason abandoned
Eligibility
Participant inclusion criteria
1. Provision of informed consent
2. Female, without child bearing potential (post-menopausal for at least one year or surgically sterile) or male, aged 50 - 85 years
3. Clinical diagnosis of mild Alzheimer's disease
4. Diagnosis of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for primary degenerative dementia of the Alzheimer's type
5. National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for Alzheimer's disease
6. Stable dose of cholinesterase inhibitors (ChEI) for at least six months or no prior treatment with ChEI. Limited treatment periods with ChEI such as days or weeks after which treatment was stopped, not regarded as having any effects on the disease.
7. Willingness and ability to complete all study-related procedures and to understand patient information
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
70
Participant exclusion criteria
1. Any other clinically significant condition or laboratory abnormality that may interfere with the patient's ability to participate in the study or the study results, as judged by the investigator
2. Electrocardiogram (ECG) changes and/or signs indicative of significant cardiovascular disease, or other conditions in which lithium treatment is contraindicated, as judged by the investigator
3. Untreated hypothyroidism
4. Concomitant use of valproic acid, memantine, neuroleptics, coumarin, anticoagulants, or non-steroidal non-inflammatory drugs (NSAIDs)
5. Salt-restricted diet
6. Clinically significant liver disease or an elevation in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin of 1.5 times the upper limit of the reference range
7. Known or suspected drug or alcohol abuse
8. Contraindications as detailed in the country-specific prescribing information for lithium
9. Participation in another drug trial within four weeks prior enrolment into this study or longer in accordance with local requirements
10. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the investigational sites)
11. Previous enrolment or randomisation of treatment in the present study
Recruitment start date
22/11/2004
Recruitment end date
29/07/2005
Locations
Countries of recruitment
Germany
Trial participating centre
Discipline of Psychiatry
Dublin
24
Ireland
Sponsor information
Organisation
AstraZeneca (Sweden)
Sponsor details
c/o Dr Peter Annas
Senior Research Scientist
AstraZeneca R & D Södertälje
Södertälje
SE-15185
Sweden
+46 8 553 290 35
peter.annas@astrazeneca.com
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
AstraZeneca (Sweden)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
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
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19573486
Publication citations
-
Results
Hampel H, Ewers M, Bürger K, Annas P, Mörtberg A, Bogstedt A, Frölich L, Schröder J, Schönknecht P, Riepe MW, Kraft I, Gasser T, Leyhe T, Möller HJ, Kurz A, Basun H, Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study., J Clin Psychiatry, 2009, 70, 6, 922-931.