neurodegeneratieve aandoeningen cognitive deterioration Dementia
Conditions
Interventions
During 3 study days, the effect of a single dose of galantamine 8 mg and
citalopram 20 mg (increased to 30 mg after 1 hr when well tolerated) will be
measured in a double-blind, randomized, placebo-
Sponsors
Centre for Human Drug Research
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Part A: Healthy subjects;• Have a body-mass index (BMI) between 18 and 34 kg/m2. • All subjects participating in this study are absent on cognitive deficits with a Mini Mental State Examination (MMSE) score between 28 and 30. • Each subject is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent. • Healthy young subjects: age 18-30. • Healthy elderly subjects: age 55-75.;Part B-D: Dementia patients • A body-mass index (BMI) between 18 and 34 kg/m2. • All patients participating in this study only have mild cognitive deficits with a Mini Mental State Examination (MMSE) score between 21 and 27. • Patients will be assessed by the treating neurologist as mentally capable of understanding the implications of study participation. • Each patient is familiar with the procedures of the study, and agrees to participate in the study program by giving oral and written informed consent. ;Part B: patients with Alzheimer's disease • The clinical diagnosis AD will be established according to the revised NINCDS-ADRDA criteria for diagnosing probable AD. • Age 55-75.;Part C: patients with frontotemporal lobe dementia • The clinical diagnosis possible FTLD will be established according the revised International Consensus Criteria for frontotemporal lobar degeneration, and supported by neuropsychological deficits and frontal and/or temporal atrophy (MRI) or hypoperfusion (ASL, SPECT). All patients will undergo extensive history taking and neurological examination in order to exclude other causes of frontal dysfunction. • Age 50-70.;Part D: patients with dementia with Lewy bodies • The diagnosis DLB will be made according to clinical criteria for probable DLB. • Age 55-75.
Exclusion criteria
Exclusion criteria: • Contra-indication to MRI scanning (pacemaker and defibrillator, intraorbital or intraocular metallic fragments, cochlear implants, one or more metal eartubes, intracranial clips, a non-removable insulin pump, a non-removable neurostimulator, a mechanical cardiac valve, an hydrocephalus pump, ferromagnetic implants, intra-uterine device, permanent make-up, tattoos above the shoulders, pregnancy, operation in 6 weeks preceding the MRI, claustrophobia, inability to lie still for a period of 20 minutes in the MRI scanner, Fear or problems during the RS-FMRI scan). • Clinically relevant abnormal history of physical and mental health as determined by medical history taking and physical examinations obtained during the screening visit (as judged by the investigator). • Other causes that can explain cognitive symptoms. • Clinically relevant abnormal laboratory results, ECG and vital signs, or physical findings at screening (as judged by the investigator). • Positive test for hepatitis B, C or HIV. • Subjects using, on average, more than 4 units of alcohol per day, and unable to refrain from alcohol use during the study days. • Subjects smoking, on average, more than 5 cigarettes per day, and unable to refrain from smoking during the study days. • Subject is a habitual and heavy consumer of caffeinated beverages (more than 6 cups of coffee or equivalent/day) at the time of the study and/or is not able to refrain from use of (methyl) xanthines (e.g. coffee, tea, cola, chocolate) during study days. • Positive drug or alcohol test at screening and/or study days. • History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study drug. • Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug or more than 4 times per year. • Donation or loss of blood (> 500 mL) within 3 months prior to screening. • Inadequate venous accessibility as judged by the physician or nurse. • Use of benzodiazepine within 48 hours before a study day. • Use of monoamine oxidase inhibitors (MAOIs) from 14 days prior to the first study day until 7 days after the last study day (incl. linezolid). • Severe asthma or obstructive pulmonary disease or active pulmonary infections (e.g. pneumonia). • Pregnancy or breast feeding. • Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject. • Use of medication in the 2 weeks prior to the first study day that is, in the opinion of the investigator, interfering with the study or the study medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Resting state network activity as measured with RS-FMRI. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Cognitive functioning as measured with different subtests of the Neurocart (a validated multimodal CNS-test battery): • Visual Analogue Scale (VAS) Bond & Lader (mood, alertness and calmness) • VAS for nausea • Adaptive tracking • Simple reaction time • Visual N-back test • Stroop test • Symbol-digit substitution test • Visual Verbal Learning Test (VVLT; 15 words) 2) Pharmacokinetics of galantamine and citalopram: • The time-course of the serum levels of galantamine and citalopram | — |
Countries
Netherlands
Outcome results
None listed