Alzheimer's Disease
Conditions
Keywords
CSF sampling, Alzheimer's disease, Amyloid beta levels
Brief summary
Modulation of beta-amyloid levels in CSF and plasma by GSK933776 in patients with mild Alzheimer's disease or mild cognitive impairment
Detailed description
This is a phase I, an open label, single dose and parallel group study to assess short term pharmacodynamics and safety of GSK933776. The effect on the beta amyloid levels will be assessed in early (MCI) and mild Alzheimer's disease (AD) patients after a single dose of GSK933776 by i.v. administration.
Interventions
BIOLOGICALGSK933776
1mg/kg dose group
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Probable mild Alzheimer's disease (MMSE 20-26) or mild cognitive impairment * Increase in total tau or p-tau in CSF * Decrease in amyloid beta in CSF * Stable dose of cholinesterase inhibitors, memantine or selegine or no treatment * Body weight less than 120 kg * Willingness to comply with contraceptive methods if self or partner is of child-bearing potential
Exclusion criteria
* Any other cause of dementia * Other significant neurologic or psychiatric illness * Hachinski Ischemia Score \>4 * More than 3 microbleeds on MRI * Type 2 diabetes not controlled by diet * Risk of cerebrovascular disease, cerebral haemorrhage or stroke * History of systemic autoimmune disease * Use of platelet anti-aggregates or anti-coagulants (Aspirin up to 325 mg/day is allowable) * Use of chronic corticosteroids * Uncontrolled hypertension in spite of antihypertensive medications * Renal or hepatic insufficiency or clinically significant anaemia * In nursing home care * Contraindications to lumbar puncture or MRI * Prior participation in therapeutic studies only after adequate wash-out period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The temporal changes of amyloid beta levels in CSF after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment | 22 hours | To compare the changes of amyloid beta levels between the baseline (9 hours) and after single dose of GSK933776 iv administration of 13 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The temporal changes of total and free amyloid beta levels in plasma after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment | Two months | — |
| The temporal changes of Tau and phosphor Tau - 181 levels in CSF after GSK933776 single dose administration in the patients with Alzheimer's disease and Mild Cognitive impairment | 22 hours | — |
| Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at multiple time points with various intervals. | three months | — |
| To assess the safety and tolerability after single dose of GSK933776 administration. | three months | The safety and tolerability measures are performed at screening, dosing day and follow up. The assessments included: • Adverse event reporting and safety laboratory data. • CNS Safety: MRI and MMSE. • CVS safety: ECG and vital signs. •Anti-GSK933776 antibodies. |
Countries
Germany, Sweden
Outcome results
None listed