We propose to conduct a study in patients with mild to moderate AD where a cholinergic challenge is given in a placebo-controlled, cross-over fashion, prior to onset of treatment with a CEI. Patients will be followed over a period of 6 months to…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
neurodegeneratieve aandoeningen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Pharmacodynamics: adaptive tracking, facial encoding and recognition task,
neuro-endocrine parameters (IGF, IGF-BP3), pharmaco-EEG, simple reaction time,
VAS Bond & Lader (mood, alertness and calmness), a VAS for nausea, pupil size,
eye movements, verbal n-back test, and the Visual Verbal Learning Test (15
words)
Pharmacokinetics: Plasma PK samples of galantamine
Treatment follow-up: MMSE, NPI, ADAS-cog/13, DAD, CDR-sum of boxes
Secondary outcome
not applicable
Background summary
Cholinesterase inhibitors (CEI*s) have been shown to enhance cognitive
functioning in patients with Alzheimer*s Disease (AD) and are used to treat
patients with AD. Only approximately 35% of patients with AD respond to
treatment with a CEI, while the other 65% of patients do not seem to respond.
It is difficult to predict which patient will respond and which will not. This
leads to many patients who are unnecessarily treated and exposed to possible
adverse drug effects. It is hypothesized that reactivity to a cholinergic
challenge may predict clinical responsiveness to cholinomimetic treatment.
Study objective
We propose to conduct a study in patients with mild to moderate AD where a
cholinergic challenge is given in a placebo-controlled, cross-over fashion,
prior to onset of treatment with a CEI. Patients will be followed over a period
of 6 months to assess how their clinical response to treatment is. The goal of
the study will be to try to correlate the measured effect on the cholinergic
challenge to the clinical response to treatment with a CEI.
Study design
Double-blind, placebo-controlled, 2-period crossover study with a cholinergic
challenge in patients with mild to moderate AD. The challenge will consist of 1
daily dose of galantamine or placebo. All patients are subsequently treated
with galantamine for a period of 6 months.
Intervention
Challenge: A single dose of galantamine 16 mg p.o. or placebo
Treatment: galantamine 8 * 24 mg/day p.o., escalation according to standard
practice
Study burden and risks
not applicable
Zernikedreef 10
Leiden 2333 CL
NL
Zernikedreef 10
Leiden 2333 CL
NL
Listed location countries
Age
Inclusion criteria
- Outpatients
- Diagnosis of probable AD (according to NINCDS-ADRDA)26
- Severity of dementia must be mild to moderate according to Clinical Dementia Rating Score (CDR of 0.5 - 2)
- No contraindication for treatment with a CEI
- Mini Mental State Exam score of 18-26 inclusive
- Assessed by the treating neurologist as mentally capable of understanding the implications of study participation
- Presence of an informant/caregiver at the information visit, signing of informed consent, and all study visits
- Signed informed consent by patient and caregiver
Exclusion criteria
- Bedridden
- Severe asthma
- Metabolic disorders interfering with absorbtion, distribution or excretion of galantamine
- Pre-existing psychiatric disease
- Other causes that can explain cognitive symptoms
- Use of neuroleptics
- Use of anticholinergics (e.g. oxybutinin, mebeverine, ipratropium(bromide))
- Use of benzodiazepine within 48 hours before a study day
- Prior or current use of a CEI (rivastigmine, galantamine, donepezil)
- Alcohol abuse (defined as use of alcohol despite significant areas of dysfunction, evidence of physical dependence, and/or related hardship due to alcohol)
- Use of recreational drugs
- Concomitant use of inhibitors of CYP2D6 (a/o kinidine, paroxetine, fluoxetine) or of CYP3A4 (a/o ketoconazol, ritonavir)
- Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-021152-25-NL |
| CCMO | NL33145.029.10 |