MCI (Mild Cognitive Impairment) due to AD (Alzheimer's disease) Mental and Behavioural Disorders
Conditions
Interventions
Following the screening period, subjects will receive certolizumab pegol (Cimzia) or placebo. Subjects will have a 50% chance of receiving Cimzia and a 50% chance of receiving placebo.
1. Subjects re
Sponsors
University of Southampton (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects will have to meet all of the following criteria at screening to enter the study: 1. All subjects must have the capacity to make an informed decision as to whether they would like to take part in this specific clinical research trial. 2. A subject can be male or female and they must be between 50 to 90 years old, inclusive. 3. A subject must have received a minimum of 7 years of formal education. 4. A subject must be able to hear, read, write and perform study neuro-psychological tests in English. 5. A subject must have adequate visual and auditory acuity to allow neuro-psychological testing, based on the research clinician?s judgement. 6. A subject must fulfil the NIA-AA criteria for the diagnosis of Mild Cognitive Impairment due to AD at the screening visit (Albert et al, 2011.) A subject must have a MOCA score of 19 to 25 inclusive at screening, at the discretion of the Principal Investigator. 7. A subject must have a study partner who spends at least 8 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. A subject must have been on a stable medication regime for more than 3 months.
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria during screening or baseline will be excluded from the study: General 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. Any contraindications to the use of certolizumab pergol as per the Summary of Product Characteristics: 1. Hyper-sensitivity to the active substance or to the excipients in the injection (sodium acetate, sodium chloride, water), 2. Active tuberculosis or other severe infections such as sepsis or opportunistic infections, 3. Moderate to severe heart failure (NYHA classes III/ IV). 2. Parkinson?s disease, Dementia with Lewy Bodies or clinically significant Parkinsonian symptoms. 3. Vascular disorder (modified Hachinski Ischaemic Scale score > 4). 4. Recent Transient Ischaemic Attack (TIA) ? within the last 3 months. 5. 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). 6. Signs of major cerebrovascular disease on the MRI performed at the screening imaging visit prior to the amyloid and microglial PET scans. 7. 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, left to the research clinician?s judgement. 8. Any of the following laboratory abnormalities at the screening visit: 8.1. Clinically significant Vitamin B12 levels less than the lower limit of normal. 8.2. Clinically significant folate levels less than the lower limit of normal. 8.3. 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. (Subjects who are successfully treated for folate, vitamin B12 or thyroxine deficiencies may be re-screened after 3 months) 9. Subjects with a previous or present history of severe medical conditions, or medical conditions which are poorly controlled, such as hypertension or diabetes, left to the research clinician?s judgement. 10. History of alcohol or drug dependence or abuse within the last 2 years. Current alcohol >35 units per week for men, or >28 units per week for women, or drug abuse, at the discretion of the research clinician. 11. Surgical intervention planned during the study period. 12. Treatment with immunosuppressive drugs including any systemic corticosteroid drugs (Topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted.) 13. Treatment with benzodiazepines within a period of three days prior to PK11195 imaging. 14. Vaccination or immunization with any live vaccine (e.g.: polio, rubella, yellow fever) or the pneumococcal vaccine within the past 30 days. 15. Pregnancy or breast feeding (women of child bearing age must have a negative HCG urine test at the start of the study and at each study visit).. 16. Severe hepatic, renal or cardiac disease. 17. Previous use of a TNFa agent. 18. Known skin photosensitivity. 19. Infection in past 4 weeks or active infection. 20. Heart fail
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To ascertain the change in microglial activation on PK 111 95 PET scans from baseline to the final imaging visit in the treatment group compared to the placebo group. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To ascertain the change in the primary cognitive outcome measure, the Montreal Cognitive Assessment, (MOCA), from baseline to final treatment visit in the treatment group compared to the placebo group. Exploratory objectives/ Outcome measures 1. To 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 in the treatment group compared to the placebo group 2. To 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 in the treatment group compared to the placebo group. 3. To ascertain the change in the Cornell Scale score from base-line to final treatment visit in the treatment group compared to the placebo group. 4. To ascertain the change in the behavioural assessment the Apathy Inventory from baseline to final treatment visit in the treatment group compared to the placebo group. 5. To ascertain the change in the behavioural assessment the Apathy Clinicians Diagnostic Criteria from baseline to final treatment visit in the treatment group compared to the placebo group. 6. To ascertain the change in the levels of plasma markers of neuro-inflammation (pro and anti-inflammatory cytokines: IL-1; IL-6, TNF-alpha, IFN-gamma, IL-4, IL-10, IL-12, IL-13; CRP, and TGF-beta) through the study, in the treatment group compared with the placebo group. 7. To study the relationship between the changes in the levels of plasma markers of neuro-inflammation (IL-1; IL-6, TNF-alpha, IFN-gamma, IL-4, IL-10, IL-12, IL-13; CRP, TGF-beta) and changes of microglial activation on PK1195 PET scan, and clinical outcomes, in the treatment group compared with the placebo group. | — |
Countries
United Kingdom
Outcome results
None listed