A Phase II Baseline Versus Treatment Study to Determine the Efficacy of Raltegravir (Isentress) in Preventing Progression of Relapsing Remitting Multiple Sclerosis as Determined by Gadolinium-enhanced MRI
There is accumulating research evidence that Human Endogenous Retrovirus (HERV) and herpes viruses (in particular Epstein-Barr Virus) are involved in the pathogenesis of multiple sclerosis. People with active MS have higher levels of HERVs than people either without MS or who have other neurological conditions. It has been shown that HERVs may produce neurotoxic proteins/antigens associated with MS activity and disease progression. This is the first clinical trial investigating the hypothesis that the antiretroviral drug raltegravir may suppress HERV activity and ameliorate progression of relapsing remitting MS. Raltegravir is an integrase inhibitor which blocks retroviral replication. A recent experimental study suggests that raltegravir may also be active against herpes viruses.
Eligible participants (see Inclusion/Exclusion Criteria) will be observed for 3 months having monthly brain Gadolinium enhanced MRIs and blood/urine/saliva sampling (baseline). Then they will be treated with raltegravir (one 400mg pill taken twice a day) for 3 months. During treatment period participants will continue to have monthly MRIs and blood/saliva/urine sampling. Participants will have monthly clinical and neurological examinations and they will complete questionnaires assessing response to treatment. Participants will have screening and study visits at The Royal London Hospital, Whitechapel. Monthly MRIs will be performed at the Institute of Neurology, UCL, Queen Square, London.
- Patients between 18-55 years of age.
- Diagnosis of MS, according to the revised McDonald Criteria 2010.
- EDSS score of 0-6.0 inclusive.
- Documented at least one relapse within the past 12 months or at least one Gd-enhanced lesion on the brain MRI detected within 3 months prior to screening date
- Gd-enhanced lesion on screening MRI (if MRI not used to meet screening criteria above).
- Female patients of childbearing potential will be expected to be on appropriate contraception (hormonal or barrier method of birth control; abstinence) from time of consent until 6 weeks after treatment discontinuation. (the repeated administration of gadolinium and MRI are not recommended during pregnancy). NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
- Females of childbearing potential must have a negative urine pregnancy test prior to every MRI scan/ within 7 days prior to being registered for protocol therapy.
- Must give written informed consent and authorize the release and use of protected health information, as required by local law.
- Able and willing to undergo blood, saliva and urine sampling at regular intervals as defined by the protocol.
- Able and willing to receive Gadolinium enhanced MRI’s at regular intervals as defined by the protocol.
- Able to comply with study requirements.
- Pregnant or breastfeeding or unwilling to use contraception.
- Treatment with immunosuppressive, immunomodulatory or experimental treatments within the last 6 months of enrolment in the study, but excluding pulsed intravenous or oral steroids for treatment of MS relapse.
- No pulsed intravenous or oral steroids in the 30 days preceding the baseline assessment.
- Patients presenting with medical disorder deemed severe or unstable by the CI such as poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, abnormal liver function tests (>2.5 times ULN) and abnormal complete blood count (in particular leukopenia, as defined by a lymphocyte count <500, neutrophil <1.5 or platelet count < 100, or thrombocytopenia < 1.5 LLN), or any medical condition which, in the opinion of the chief investigator, would pose additional risk to the patient.
- Presence of human immunodeficiency virus antibodies.
- Patients receiving proton pump inhibitors (e.g. omeprazole/esomeprazole)
- Patients with active hepatitis B or/and C with liver function tests >2.5 times ULN
- Exposure to any other investigational drug within 30 days of enrolment in the study.
- Prior history of malignancy unless an exception is granted by the Chief Investigator.
- History of uncontrolled drug or alcohol abuse within 6 months prior to enrolment into the study.
- Patients treated with Rifampicin in past four weeks.
ClinicalTrials.gov Identifier: NCT01767701
“Who would of thought that when we launched The Charcot Project a year ago that we would have a trial off the ground in just over 12 months. Without Prof. Julian Gold’s dedication energy, persistent and organisational abilities this would not have been possible. We would also like to thank our initial sponsors Mr and Mrs Anon. and AIMS2CURE for supporting the launch of The Charcot Project despite the widespread scepticism of the viral hypothesis in the field of MS. Thanks to Merck for taking a risk on us delivering this study. Hopefully, in 2 years time this trial will cause the paradigm shift I have been predicting will occur for some time! We have had over 15 grants turned down around the viral hypothesis of MS, so getting this one off the ground is very special indeed. We would also like to acknowledge all the scientists in the field who have been working so diligently on HERVs and MS, in particular Dr. Hervé Perron, without their persistence we would not have been able to make the scientific case for this study.”