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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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ISRCTN |
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Last refreshed on:
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13 January 2015 |
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Main ID: |
ISRCTN72046462 |
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Date of registration:
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02/07/2008 |
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Prospective Registration:
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No |
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Primary sponsor: |
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Public title:
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A randomised, single-blinded, placebo-controlled, multicentre study to investigate the pharmacodynamic effects of lithium on glycogen synthase kinase-3 (GSK-3) activity in patients with Alzheimer's disease
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Scientific title:
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Date of first enrolment:
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22/11/2004 |
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Target sample size:
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70 |
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Recruitment status: |
Completed |
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URL:
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http://isrctn.com/ISRCTN72046462 |
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Study type:
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Interventional |
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Study design:
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Randomised, single-blind, placebo controlled, parallel-group multicentre study (Treatment)
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Phase:
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Countries of recruitment
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Germany
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Contacts
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Name:
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Harald
Hampel |
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Address:
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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
24
Dublin
Ireland |
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Telephone:
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+353 (0)1 896 3706 |
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Email:
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harald.hampel@tcd.ie |
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Affiliation:
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Key inclusion & exclusion criteria
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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
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
Age minimum:
Age maximum:
Gender:
Both
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Health Condition(s) or Problem(s) studied
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Alzheimer's disease
Nervous System Diseases
Alzheimer's disease
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Intervention(s)
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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)
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Primary Outcome(s)
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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
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Secondary Outcome(s)
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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
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Secondary ID(s)
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D0200C00001
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Source(s) of Monetary Support
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AstraZeneca (Sweden)
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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