Mild cognitive impairment (MCI) due to Alzheimer’s disease (AD). Nervous System Diseases Alzheimer disease
Conditions
Interventions
Participants in the study will be given either:
1. A 50mg once weekly subcutaneous injection of etanercept for 52 weeks
2. A subcutaneous injection of the placebo
Sponsors
University of Southampton
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Capacity to make an informed decision as to whether they would like to take part in this specific clinical research trial 2. Male or female aged between 50-90 3. Minimum 7 years formal education 4. Be able to hear, read, write and perform study neuro-psychological tests in English 5. Adequate visual and auditory acuity to allow neuro-psychological testing, based on the research clinician’s judgement 6. Fulfil the NIA-AA criteria for the diagnosis of MCI due to AD at the screening visit. Participants must have a MOCA score of 19 to 25 inclusive at screening, at the discretion of the Principal Investigator 7. Have a study partner who spends at least eight hours a month with the subject. The study partner may be a close friend or a neighbour and not necessarily a close relative, spouse, son or daughter, and should be present at all visits. Every effort should be made to ensure that the study partner will be the same throughout the study. If it becomes necessary for the study partner to change, the new study partner must satisfy the requirements of this criterion and the change of study partner must be clearly documented 8. Been on a stable medication regime for more than 3 months prior to screening 9. Women of child bearing potential must use adequate contraception to prevent pregnancy and continue its use for at least four weeks after the last study dose
Exclusion criteria
Exclusion criteria: 1. Inability or refusal to provide informed consent from subject or study partner 2. Absence of study partner 3. Unlikely to cooperate in the study, not able to attend scheduled examinations and visits, or not able to follow study instructions 4. Participation in another study with administration of any investigational drug in the previous 3 months or already enrolled in another study Medical and therapeutic criteria: 1. Parkinson’s disease, Dementia with Lewy Bodies or clinically significant Parkinsonian symptoms 2. Vascular disorder (modified Hachinski Ischaemic Scale score >4) 3. Recent Transient Ischaemic Attack (TIA) (within the last 3 months) 4. Signs of major cerebrovascular disease on MRI or CT scan prior to entry into study (i.e. evidence of an established cortical or basal ganglia infarct) 5. Signs of major cerebrovascular disease on the MRI performed at the screening imaging visit prior to the amyloid and microglial PET scans 6. Any other previous or ongoing chronic or recurrent disease of the central nervous system, including demyelinating disease or psychiatric diseases, that may have an impact on cognitive performance 7. Any of the following laboratory abnormalities at the screening visit: 7.1. Clinically significant Vitamin B12 levels less than the lower limit of normal 7.2. Clinically significant folate levels less than the lower limit of normal 7.3. Clinically significant thyroid-stimulating hormone (TSH) levels greater than the upper limit of normal and a clinically significant free thyroxine (FT4) level lower than the lower limit of normal (participants who are successfully treated for folate, vitamin B12 or thyroxine deficiencies may be re-screened after 3 months) 8. Subjects with a previous or present history of severe medical conditions, or medical conditions which are poorly controlled, such as hypertension or diabetes 9. History of alcohol or drug dependence or abuse within the last 2 years. Current alcohol >35 units/week for men or >28 units/week for women, or drug abuse 10. Surgical intervention planned during the study period 11. Treatment with immunosuppressive drugs including any systemic corticosteroid drugs (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) 12. Treatment with benzodiazepines within a period of three days prior to [11C] (R)-PK-111-95 PET scans imaging 13. Vaccination or immunisation with any live vaccine (e.g. polio, rubella, yellow fever) within the past 30 days 14. Pregnancy or breast feeding 15. Severe hepatic, renal or cardiac disease 16. Previous use of a TNFa agent 17. Known skin photosensitivity 18. Infection in past 4 weeks or active infection 19. Heart failure: New York Heart Association (NYHA) Grade 3-4 20. History of blood disorders or current WCC = 3.5 x 109/l; platelet count = 100x109/l; Hb = 10g/dl 21. Active or latent tuberculosis 22. Rheumatoid arthritis; psoriasis; psoriatic arthritis or ankylosing spondylitis 23. Septic arthritis in past 12 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Ascertain the change in microglial activation on [11C] (R)-PK-111-95 PET scans from base-line to the final imaging visit in the treatment group compared to the placebo group. The imaging related outcome measures (microglial activation and cortical amyloid load) will be done at the screening image visit and at the final imaging visit, one week before the end of the treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| The neuro-psychological testing related outcome measures will be done at base-line, Visit (V) 1, and repeated at V3 (13 weeks into treatment period), V4, (26 weeks), V5 (39 weeks), V6, (52 weeks on treatment, end of treatment period). Procedures carried out: PET scans x 4; MRI scans x 2; CXR x 1; blood tests x 10; urine tests x 8; ECG x 1, and as required; optional LP x 1; study injection, sub-cutaneous, x 53; physical examination x 8; neuro-psychological testing x 6: 1. Ascertain the change in the primary cognitive outcome measure, the Montreal Cognitive Assessment (MOCA) from baseline to final treatment visit 2. Ascertain the change in cortical amyloid load on AMYVID PET scans from base-line to the final imaging visit Exploratory objectives: 1. Ascertain the change in the first of the exploratory cognitive outcome measures, the Repeatable Battery for the Assessment of Neuro-psychological Status, (RBANS), from baseline to final treatment visit 2. Ascertain the change in the second of the exploratory cognitive outcome measures, the Free and Cued Recall Selective Reminding Test with Immediate Recall (FCSRT-IR), from baseline to final treatment visit 3. Ascertain the change in the Cornell Scale score from base-line to final treatment visit 4. Ascertain the change in the behavioural assessment the Apathy Inventory from baseline to final treatment visit 5. Ascertain the change in the behavioural assessment the Apathy Clinicians Diagnostic Criteria from baseline to final treatment visit 6. Ascertain the change in the levels of plasma markers of neuro-inflammation (pro and anti-inflammatory cytokines: IL-1; IL-6, TNF-a, IFN-?, IL-4, IL-10, IL-12, IL-13; CRP, and TGF-ß). The neuro-inflammatory markers for the neuro-inflammatory explorative outcome measures will be taken at the two imaging visits and at V3, V4, and V5. | — |
Countries
England, United Kingdom
Outcome results
None listed