Clinical trial NCT01424436: Modulation of Abeta Levels by GSK933776 in Alzheimer's Disease Patient
Official title: Modulation of Beta-amyloid Levels in CSF and Plasma by GSK933776 in Patients With Mild Alzheimer's Disease or Mild Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Keywords: CSF sampling
Alzheimer's disease
Amyloid beta levels
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-08-29
Enrollment: 19
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 22 hours
Secondary outcomes:
measure: 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
timeFrame: Two months
measure: 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
timeFrame: 22 hours
measure: Estimated pharmacokinetic parameters of AUC, Cmax and Tmax in CSF and plasma at multiple time points with various intervals.
timeFrame: three months
measure: To assess the safety and tolerability after single dose of GSK933776 administration.
timeFrame: three months
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Aachen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Malmö
country: Sweden
facility: GSK Investigational Site
city: Stockholm
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Andreasen N, Simeoni M, Ostlund H, Lisjo PI, Fladby T, Loercher AE, Byrne GJ, Murray F, Scott-Stevens PT, Wallin A, Zhang YY, Bronge LH, Zetterberg H, Nordberg AK, Yeo AJ, Khan SA, Hilpert J, Mistry PC. First administration of the Fc-attenuated anti-beta amyloid antibody GSK933776 to patients with mild Alzheimer's disease: a randomized, placebo-controlled study. PLoS One. 2015 Mar 19;10(3):e0098153. doi: 10.1371/journal.pone.0098153. eCollection 2015.
citation: Leyhe T, Andreasen N, Simeoni M, Reich A, von Arnim CA, Tong X, Yeo A, Khan S, Loercher A, Chalker M, Hottenstein C, Zetterberg H, Hilpert J, Mistry P. Modulation of beta-amyloid by a single dose of GSK933776 in patients with mild Alzheimer's disease: a phase I study. Alzheimers Res Ther. 2014 Apr 9;6(2):19. doi: 10.1186/alzrt249. eCollection 2014.