Frontotemporal lobar degeneration, including behavioural variant of frontotemporal dementia (bvFTD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS)/corticobasal degeneration (CBD) Nervous System Diseases Frontotemporal lobar degeneration
Conditions
Interventions
The protocol includes several experiments investigating different drugs and patient groups, however for the purpose of ISRCTN registration we describe the two experiments (experiments A and B) using t
Sponsors
Cambridge University Hospitals NHS Foundation Trust and University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients in the principal study: 1. Frontotemporal dementia including subtypes diagnosed by current consensus criteria for behavioural variant or language variants Patients in secondary studies: 2. Motor neuron disease with or without associated FTD or FTLD-related tau disorders (progressive supranuclear palsy or corticobasal degeneration, by consensus clinical diagnostic criteria) Healthy controls: 3. No major neurological or psychiatric disorder 4. Aged 20-80 years 5. English-speaking
Exclusion criteria
Exclusion criteria: Current participant exclusion criteria as of 19/06/2024: Participant exclusion criteria 1. Clinically significant current depression 2. Contraindications to MRI or MEG 3. Contraindications to pharmacological challenges, including: 3.1. Ischemic heart disease or significant cardiac rhythm abnormalities, 3.2. Current epilepsy 3.3. Pregnancy 3.4. Adverse drug reactions to citalopram, memantine, tiagabine, zolpidem or closely related drugs (according to experiment) 3.5. Other major psychiatric disorders including mania or schizophrenia 3.6. Known hepatic or renal failure (moderate or severe) Previous participant exclusion criteria: 1. Clinically significant current depression 2. Contraindications to MRI or MEG 3. Contraindications to pharmacological challenges, including: 3.1. Ischemic heart disease or significant cardiac rhythm abnormalities, 3.2. Current epilepsy 3.3. Pregnancy 3.4. Adverse drug reactions to citalopram, memantine, tiagabine or closely related drugs (according to experiment) 3.5. Other major psychiatric disorders including mania or schizophrenia 3.6. Known hepatic or renal failure (moderate or severe)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 19/06/2024: 1. Motor learning assessed using combined magnetoencephalography (MEG)/electroencephalogram (EEG) and behavioural responses, approx. 2 hours after the drug or placebo is taken. 2. Cortical responses to an auditory oddball paradigm assessed using combined MEG/EEG approx. 2 hours after the drug or placebo is taken. 3. Resting state brain responses assessed using combined MEG/EEG approx. 2 hours after the drug or placebo is taken. 4. Reaction times and response inhibition using combined magnetoencephalography (MEG)/electroencephalogram (EEG) and behavioural responses, approx. 2 hours after the drug or placebo is taken. Previous primary outcome measures: 1. Motor learning assessed using combined magnetoencephalography (MEG)/electroencephalogram (EEG) and behavioural responses after a change in condition on the afternoon after the morning when the drug or placebo is taken 2. Cortical responses to an auditory oddball paradigm assessed using combined MEG/EEG on the afternoon after the morning when the drug or placebo is taken 3. Resting state brain responses assessed using combined MEG/EEG on the afternoon after the morning when the drug or placebo is taken | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. ?-aminobutyric acid (GABA) levels assessed using magnetic resonance imaging (MRI) scanning. This is an MRI scan with structural MRPAGE, DWI, T2, PD sequences, arterial spina labelling, resting BOLD-sensitive echo-planar imaging and a magnetic resonance spectroscopy sequence for GABA. Shorter scans are possible, to obtain just a structural MRI, based on discussion between participants, their carers, and the study team. This scan is conducted at baseline and can take 60-90 minutes; however, participants can opt for a shorter 15-min scan only 2. General background data on the distribution and severity of cognitive deficits assessed using a neuropsychological testing battery. These tests can be carried out on clinic or home visits, or on the study days and are obtained just once as a measure of severity of deficit, or on both days as a measure of drug effect. The battery includes: 2.1. Addenbrooke’s Cognitive Exam- revised (ACE-r) 2.2. INECO Frontal Screening (IFS). 2.3. Frontal Assessment Battery (FAB). 2.4. Dimensional Apathy Scale (DAS) 2.5. Hayling Sentence Completion Test 2.6. Cambridge Questionnaire for Apathy and Impulsivity (CAM-QUAIT) 2.7. Carers Behavioural Inventory (CBI, can also be done at home by the carer) 3. Wellbeing, alertness and fatigue related symptoms assessed using a Visual Analogue Scale and completed completed before the drug/placebo and at the end of the day before going home, i.e. twice a day on study days | — |
Countries
England, United Kingdom
Contacts
Public ContactLaura Hughes
Outcome results
None listed