Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis
Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis
The purpose of this study is to determine whether raltegravir is effective 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 at Queens Square, London.
Inclusion Criteria:

 -  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.

 Exclusion Criteria:

 -  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.