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Contact Information:

Prof Clive Holmes
+44 (0)23 80 475216
c.holmes@soton.ac.uk


Study Location:

Memory Assessment & Research Centre
Southampton
SO30 3JB


A study examining the effect of Cimzia on inflammation in the brain

Stopped

Open to: All Genders

Age: Senior

Medical Conditions

MCI (Mild Cognitive Impairment) due to AD (Alzheimer's disease)


Study summary

Background and study aims
Alzheimer’s disease (AD) is the most common type of dementia. It’s a condition that results in a loss of mental ability due to the gradual death of brain cells. Brain inflammation may play a role in the development and progression of AD and poor memory in general. The TNF (tumour necrosis factor) alpha protein controls the body’s inflammatory response; it is increased in AD and is linked with progression of the disease. Cimzia is a medicine that is used to treat inflammatory diseases, such as rheumatoid arthritis by reducing the inflammatory response. Here, we want to find out if Cimzia reduces brain inflammation.

Who can participate?
Adults aged between 50-90 that have a mild cognitive impairment due to AD. They must also have a study partner – anyone who spends more than 8 hours a month in their company.

What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 are given Cimzia for up to a year. Those in group 2 are given a placebo for the same time period. The drug is given as an injection once every two weeks; participants and their study partners receive training on how to administer it. Each participants general health and memory is checked over a series of 7 sessions over the course of the study. Tests include blood and memory tests, a chest X-ray, MRI scan of the brain and PET scan. A PET scan is also referred to as a brain scan. Here, we give each participant a radioactive tracer. This is an extremely small dose of a drug that is radioactively tagged so that its movements around the body can be seen. The tracer is injected and the brain then looked at by the PET scan.

What are the possible benefits and risks of participating?
Like all medicines, Cimzia can cause side effects, although not everybody gets them. They include skin rashes, fever, allergic reactions, and reduced production of blood cells. There have been reports of cancers which may be related to taking Cimzia. These include cancers of the blood and lymphatic system (including lymphoma, which is a tumour of the lymph nodes, and leukaemia), solid organ tumours and non-melanoma skin cancers. Cimzia may decrease the participants ability to fight infection. Each participant is monitored carefully during the study for possible side effects.

Where is the study run from?
The Memory and Assessment Research Centre (MARC) at Moorgreen Hospital (Southampton)

When is the study starting and how long is it expected to run for?
November 2014 to November 2017

Who is funding the study?
1. European Union FP7 (Grant agreement no: 278850)
2. Union Chimique Belge (UCB) pharmaceuticals (Belgium)

Who is the main contact?
Professor Clive Holmes
c.holmes@soton.ac.uk

In MCI (mild cognitive impairment) due to AD (alzheimer’s disease), systemic inflammation and elevated systemic levels of TNF-alpha cause partially activated, or primed, microglial cells, to become fully activated, which can be modulated by the administration of a peripheral TNF-alpha antibody, certolizumab pergol (Cimzia).


Double-blind randomised placebo-controlled study

Key dates

The recruitment start and end dates are as follows:

01 Nov 2014

01 Nov 2017

Study type

Interventional

Intervention Type : Drug
Intervention Name : certolizumab pergol
Intervention Description : 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 receiving Cimzia will receive a loading dose of 400mg of certolizumab pegol at base-line, week 2 and week 4. The loading dose will be given as two subcutaneous injections of 200mg each.

2. Subjects receiving placebo will receive an imitation loading dose of placebo at base-line, week 2 and week 4, given as two subcutaneous injections of the placebo.

The subjects will attend for a safety visit at week 4, after receiving the third of the loading doses of Cimzia or placebo. Thereafter, the subjects receiving Cimzia will receive a two weekly maintenance dose of 200mg of certolizumab pegol, given as a two weekly subcutaneous injection of 200mg of certolizumab pegol from week 6 to week 52 inclusive, and the subjects receiving placebo will receive an imitation two weekly subcutaneous injection of the placebo from week 6 to week 52, inclusive.

Subjects who receive the final dose of the study medication at week 52 will be asked to attend a follow up visit at week 54, for a full safety check. Subjects with unresolved Adverse Reactions or unresolved Serious Adverse Events will be followed up until the problems have resolved, by means of unscheduled clinic visits and/or telephone consultations, as clinically indicated.


Who can take part?

You can take part if:


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.




You may not be able to take part if:

Subjects meeting any of the following criteria during screening or baseline will be excluded from the study:General criteria1. 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 criteria1. 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 TNFα agent.18. Known skin photosensitivity.19. Infection in past 4 weeks or active infection.20. Heart failure: New York Heart Association (NYHA) Grade 3-4.21. History of blood disorders or current WCC ≤ 3.5 x 109/l; platelet count ≤ 100x109/l; Hb ≤ 10g/dl.22. Active or latent tuberculosis.23. Rheumatoid arthritis; psoriasis; psoriatic arthritis or ankylosing spondylitis.24. Septic arthritis in past 12 months.25. Sepsis of prosthesis in past 12 months. 26. Chronic leg ulcers.27. Indwelling urinary catheter.28. Pulmonary fibrosis.29. History of neoplasms / malignancies in past 3 years.30. Pre-malignant conditions including Barrett’s oesophagus; cervical dysplasia; large bowel polyps. 31. Other clinically significant abnormality on physical, neurological, ECG or laboratory examination that could compromise the study evaluations or be detrimental to the patient during the course of the study. 32. Use of experimental medications for AD, or any other investigational medication or device, within 60 days. Patients who have been involved in a monoclonal antibody study are excluded unless it is known that they were receiving placebo in that trial.

Imaging exclusion criteria.

33. Subjects with significant cortical or basal ganglia infarct or other significant pathology found on MRI brain scan.34. Subject with a negative Amyloid PET scan.


Where can I take part?

Below are the locations for where you can take part in the trial.

  • Memory Assessment & Research Centre
    Southampton
    SO30 3JB

Funders/Sponsors


The study is sponsored by University of Southampton (UK) and funded by European Union FP7 (Grant agreement no: 278850); Union Chimique Belge (UCB) pharmaceuticals (Belgium) .



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for Trial ID: ISRCTN43889760

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