Alzheimer's Disease Nervous System Diseases Alzheimer's Disease
Conditions
Interventions
Single-centre double-blind placebo-controlled two-period crossover intervention study with a cholinergic challenge in patients with mild to moderate Alzheimer's Disease.
The challenge
Sponsors
Centre for Human Drug Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Clinical diagnosis of AD 2. Mini Mental State Examination (MMSE) score ranging from 18 to 26 3. Clinical Dementia Rating (CDR) score between 0.5 and 2.0
Exclusion criteria
Exclusion criteria: 1. Previous or current use of CEIs, anticholinergic drugs or neuroleptics 2. Contraindications for the use of CEIs 3. Use of benzodiazepines 48 hours prior to the study days 4. History of psychiatric disorders
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Long-term clinical response to galantamine assed using pharmacodynamic parameters measured by the NeuroCart test battery, including: 1. The N-back tests evaluated working memory 2. Adaptive tracking measured sustained attention 3. Eye-hand coordination 4. Simple Reaction Time task measured the attention and speed of information processing 5. Visual analogue scale according to Bond and Lader assessed changes in subjective states 6. Facial encoding and recognition task episodic memory 7. Visual verbal learning test (VVLT) covered the scope of learning behaviour (i.e., acquisition, consolidation, storage and retrieval 8. Pharmaco-electroencephalography 9. Eye movements and pupil size were used to determine drug effects on neurophysiological and autonomous system function. Pupil size, eye movements, adaptive tracking, simple reaction time, visual analogue scales and N-back tests were performed twice at baseline, and at 1, 2, 4, and 5 hours following galantamine or placebo administration. The VVLT was executed 1.5 hours after drug-administration (immediate recall) and 3.0 hours following drug-administration (delayed recall and recognition). The facial recognition task was performed at baseline and 2.5 hours after dosage. Pharmaco-EEG measurements were performed at baseline and 0,5, 1, 1,5, 2, 4 and 5 hours post galantamine administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmacokinetic parameters: 1.1 Plasma galantamine concentrations via an indwelling catheter at baseline and at 0,25, 0,5, 1, 1,5, 2, 2,5, 3,5 and 5 hours following drug administration. 2. Safety assessments by blood sampling: 2.1 Vital signs measurements 2.2 12-lead ECG 2.3 Urinalysis 2.4 Urinary drug screen 2.5 Haematology 2.6 Biochemistry All safety assessments were performed at baseline and additionally at 0.5, 1.5 and 5.0 hours post- drug administration. 3. Clinical outcomes assessments: 3.1 The Alzheimer's Disease Assessment (ADAS)-cog subscale was used to evaluate the severity of cognitive and non-cognitive behavioral dysfunction characteristic for AD patients 3.2 Cognitive performance of subjects was assessed by the Clinical Dementia Rating Scale (CDR) in which statements related to the following 6 domains are scored: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care 3.3 The Disability Assessment in Dementia (DAD) scale was used to evaluate basic and instrumental activities of daily living (ADL) 3.4 The Mini Mental State Examination (MMSE) is a brief 30-point questionnaire test which was used to screen for cognitive impairment 3.5 With the Neuropsychiatric Inventory (NPI) diverse behavioural and psychological symptoms of dementia were measured 3.6 The ADAS-cog, CDR, DAD, MMSE and NPI were carried out after two and 6 months of treatment | — |
Countries
Netherlands, Romania
Outcome results
None listed