Amyloid imaging in Alzheimer's disease, frontotemporal dementia and healthy volunteers
- Conditions
- Nervous System DiseasesFrontotemporal dementia and Alzheimer's diseaseAlzheimer's disease
- Registration Number
- ISRCTN58435532
- Lead Sponsor
- Avid Radiopharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 40
Subjects who meet all of the following criteria are eligible to enrol in the arm of this trial reserved for patients with probable AD:
1. Male or female patients, at least 50 years of age, with probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) criteria
2. Patients with mild/moderate dementia as evidenced by a Mini-Mental State Examination (MMSE) score ranging from 10 to 24, boundaries included, at screening
3. Patients whose history of cognitive decline has been gradual in onset and progressive over a period of at least 6 months. Evidence should be present indicating sustained memory deterioration in an otherwise cognitively normal patient, plus additional impairment in another cognitive function such as: orientation, judgment and problem solving, or functioning in personal care.
4. Patients who live with or have regular visits from a responsible caregiver willing to provide information about the patient
5. Patients who give informed consent by signing a UK Multicentre Research Ethics Committee (MREC) approved informed consent prior to any study procedures. If the patient is incapable of giving informed consent, the caregiver may consent on behalf of the patient (the patient must still confirm assent). The consent procedure will be performed in accordance with the Mental Capacity Act 2005.
Subjects who meet all of the following criteria are eligible to enrol in the arm of this trial reserved for patients with FTD:
1. Males or females at least 45 years of age
2. Meet the consensus criteria for frontotemporal lobar degeneration and have mild to moderate disease severity. Clinical and neuropsychological criteria will be applied and will include only patients with the clinical phenotypes of behavioural-dysexecutive FTD. Clinical and neuropsychological features are obligatory, while patients can also be included if structural imaging findings are supportive of the diagnosis or neutral (not suggesting an alternative diagnosis). Functional imaging findings will not be considered prior to patient inclusion.
3. Have a caregiver who can report on their mental status and Activities of Daily Living (ADL)
4. Patients who give informed consent by signing a UK Multicentre Research Ethics Committee (MREC) approved informed consent prior to any study procedures. If the patient is incapable of giving informed consent, the caregiver may consent on behalf of the patient (the patient must still confirm assent). The consent procedure will be performed in accordance with the Mental Capacity Act 2005.
Subjects who meet all of the following criteria are eligible to enrol in this trial as normal healthy volunteers:
1. Healthy male or female at least 45 years of age, with no evidence of significant cognitive impairment by history and psychometric testing
2. MMSE greater than or equal to 29, and are cognitively normal by informant report and on the psychometric test battery at screening
3. Volunteers who give informed consent by signing a UK Main Research Ethics Committee (MREC) approved informed consent prior to any study procedures
1. Neurodegenerative disorders other than AD or FTD as appropriate, including, but not limited to Parkinson's disease, Huntington's disease, Down's syndrome, Creutzfeldt-Jacob disease, normal pressure hydrocephalus, and progressive supranuclear palsy
2. Have now or have had a diagnosis of other dementing/neurodegenerative disease (e.g. Parkinson's disease, dementia with Lewy bodies, Lewy body variant AD, etc.)
3. Have now or have had a diagnosis of mixed dementia
4. Cognitive impairment or significant residual findings on magnetic resonance imaging (MRI) resulting from:
4.1. Acute cerebral trauma or post-traumatic brain injury, subdural haematoma, or injuries secondary to chronic trauma (e.g., sequella from boxing)
4.2. Hypoxic cerebral damage regardless of aetiology; e.g., cognitive or neurological deficits resulting from cardiac arrest or cardiac surgery, anaesthesia, or severe self-poisoning episode, secondary to severe hypovolaemia (orthostatic hypotension should not lead to exclusion)
4.3. Vitamin deficiency states documented by medical history such as folate, vitamin B12 and other B complex deficiencies; e.g., thiamine deficiency in Korsakoff's syndrome (patients taking regular B12 and folate are not necessarily excluded)
4.4. Cerebral infection including abscess, syphilis, meningitis, encephalitis or acquired immune deficiency syndrome (AIDS)
4.5. Primary or metastatic cerebral neoplasia
4.6. Significant endocrine or metabolic disease; e.g., thyroid, parathyroid, or pituitary disease, Cushing's syndrome, or severe renal failure
4.7. Mental retardation
Before enrolling a patient with past or current history of any of the above conditions, the investigator must contact the sponsor to discuss whether the condition could have contributed to the cognitive impairment.
5. Clinically significant infarct or possible multi-infarct dementia as defined by the NINCDS criteria, including:
5.1. A history of a significant cerebrovascular event resulting in a physical or neurological deficit that may confound the assessment of the patient's intellectual function
5.2. Multiple focal signs on neurologic examination indicative of multiple ischaemic episodes
5.3. One or more of the following findings on a MRI scan:
5.3.1. Multiple (two or more) infarcts or white matter lacunes
5.3.2. A single large infarct or a strategically placed infarct in the angular gyrus, the thalamus, the basal forebrain, the posterior cerebral artery (PCA), or anterior cerebral artery (ACA) territory
5.3.3. Extensive periventricular white matter disease. Leukoaraiosis (periventricular white matter, low attenuation) should be distinguished from multiple infarctions. Leukoaraiosis is common in normal individuals and patients with AD. White matter deterioration should not result in exclusion unless it is abnormal and widespread, e.g., Binswanger's disease.
6. Any evidence on screening MRI, computed tomography (CT), or other biomarker studies that suggests an alternate aetiology (other than probable AD in patients with AD, FTD in patients with clinically defined FTD) for cognitive deficit; or in the case of cognitively normal controls any evidence on screening MRI, CT, or other biomarker studies that suggests the presence of AD, FTD or other significant neuropathology.
7. Current clinically significant psychiatric disease, as judged by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria, particularly current major depression or schizophrenia. Pati
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Evaluation of FDG PET imaging (FDG patients only)<br>2. Evaluation of amyloid imaging (FDG and AD patients)<br><br>Florpiramine F 18 images will be evaluated qualitatively and quantitatively. Images will be visually examined and will be classified as Aß+ (amyloid positive, AD-like) or Aß- (amyloid negative, not AD). Images will be evaluated quantitatively and qualitatively. Parametric statistics will be used to compare the SUV/SUVR in the various brain regions for patients with AD, patients with FTD and cognitively healthy volunteers to evaluate the hypothesis that cortical to cerebellar SUVR will be higher in target regions of patients with AD than in FTD patients. The primary analysis will contrast (t-test) precuneus to cerebellar SUVR in patients with AD versus patients with FTD. Finally the blinded reader interpretation (with and without sequential unblinding) will be compared to the clinical diagnosis for subjects with AD, FTD, and cognitively healthy volunteers.
- Secondary Outcome Measures
Name Time Method o secondary outcome measures