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Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis (INSPIRE)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Gavin Giovannoni, Queen Mary University of London
ClinicalTrials.gov Identifier:
NCT01767701
First received: January 7, 2013
Last updated: May 24, 2017
Last verified: May 2017
January 7, 2013
May 24, 2017
April 2013
September 2014   (Final data collection date for primary outcome measure)
The Number of New or Recurrent Gd-enhancing Lesions That Appear on Brain T1-weighted MRI [ Time Frame: Baseline and at 6 months ]

Demonstrate in subjects with relapsing remitting multiple sclerosis a reduction in the number of new or recurrent Gd-enhancing lesions that appear on brain T1-weighted MRI over the period of treatment with raltegravir, compared to baseline.

Within patient change in number of lesions was calculated by subtracting the after treatment period (3 months) minus before treatment period (3 months).

The Number of New or Recurrent Gd-enhancing Lesions That Appear on Brain T1-weighted MRI [ Time Frame: Baseline and monthly until month 6 post baseline ]
Complete list of historical versions of study NCT01767701 on ClinicalTrials.gov Archive Site
  • The Cumulative Number of New or Enlarging T2 Weighted Lesions on Brain MRI. [ Time Frame: Baseline and monthly for 6 months ]

    Demonstrate a reduction in the cumulative number of new or enlarging T2 weighted lesions on brain MRI over the period of treatment with Raltegravir compared with baseline.

    Within-patient changes in lesion count calculated after-before.

  • Change in Score on Multiple Sclerosis Functional Composite (MSFC). This a Composite Score Based on the Measurement of Time in Seconds for the Three Separate Measurements. [ Time Frame: Baseline and monthly until month 6. ]
    Explore preliminary clinical responses in relapsing-remitting multiple sclerosis subjects treated with Raltegravir, compared with baseline as measured by Patient Reported Outcomes (Questionnaires). The MSFC is a composite score consisting of the standardly derived composite score from 9-hole peg test (9HPT), timed walk and PASAT scores. 9HPT is measured as timed speed to complete the task; higher scores indicate less disability. The 25-foot walk is measured as timed speed; higher scores indicate less disability. The Paced Auditory Serial Addition Test (PASAT) The PASAT is a measure of cognitive function that assesses auditory information processing speed and flexibility, as well as calculation ability. It is a timed speed test measured in seconds. In the PASAT a lower score indicates less disability.
  • Changes in Kurtzke Extended Disability Status Scale (EDSS) Score [ Time Frame: Baseline and monthly to month 6 ]

    The Kurtzke Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis. The scale has been developed by John F. Kurtzke. The EDSS quantifies disability in eight Functional Systems (FS) and allows neurologists to assign a Functional System Score (FSS) in each of these. 0 = Normal 1-1.5 = No disability, but some abnormal neurological signs 2-2.5 = Minimal disability 3-4.5 = Moderate disability, affecting daily activities, but you can still walk. A lower score indicates less disability.

    5-8 = More severe disability, impairing your daily activities and requiring assistance with walking 8.5-9.5 = Very severe disability, restricting you to bed 10 = Death EDSS scores were measured monthly over 6 months and the mean of the measurements for the first three months (baseline) was recorded to use calculate the change from baseline compared with the mean of measurements taken monthly during the second three months (treatment).

  • Cumulative Number of Gd-T1 Enhancing Lesions [ Time Frame: At Baseline and monthly for 6 months ]
    This measure is the number of gadolinium-enhancing T1 lesions as determined by MRI taken on the monthly basis during the six months of the study.
  • Percent of Subjects With Scans Free From Enhancing Lesions in Raltegravir Treated Subjects vs. Baseline [ Time Frame: Baseline to 6 months ]
    This measure is the cumulative percentage of subjects who had scans free from Gd enhancing lesions during the first three months (baseline) compared with the second three months (treatment). These percentages are expressed as a total percentage for the baseline and for the treatment periods.
  • The cumulative number of new or enlarging T2 weighted lesions on brain MRI [ Time Frame: Baseline and monthly for 6 months ]
  • Change in score on Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: Baseline and monthly until month 6. ]
  • Changes in Kurtzke Extended Disability Status Scale (EDSS) Score [ Time Frame: Baseline and monthly to month 6 ]
  • Cumulative Number of Gd-T1 Enhancing Lesions [ Time Frame: At Baseline and monthly for 6 months ]
  • Percent of Subjects With Scans Free From Enhancing Lesions in Raltegravir Treated Subjects vs. Baseline [ Time Frame: At baseline and monthly for 6 months ]
  • Mean Number of Adverse Events Per Patient [ Time Frame: Screening to six months ]

    This outcome will be assessed by blood and urine sampling; collection of patient reported symptoms and neurological and physical exams.

    This measure is the total number of adverse events recorded for each type of event during the study period. The number of participants is 31 which is the number screened and enrolled in the study. Eleven participants did not meet the criterion for baseline i.e. having a gadolinium enhancing lesion on MRI at the baseline visit and therefore did not continue to the baseline observation period. The adverse events for the 11 participants who did not begin the study observation period were recorded during the screening period and added to the 20 participants who were studied during the 6 months of the study. Adverse events are recorded as total number during the study period. Each patient may have had more than one adverse event.

  • Effect of Raltegravir Therapy on Specific Inflammatory Marker of MS Activity. [ Time Frame: Baseline to 6 months ]
    Measured by Human C-Reactive Protein (HCRP) which is a measure of general inflammation. The higher the value the more inflammatory response is present. The HCRP was measured monthly for six months. The mean value for the baseline three months was compared with the mean value taken for the second (treatment) three months.
  • Number of adverse events [ Time Frame: Continuously throughout the study ]
    This outcome will be assessed by blood, urine and saliva sampling; collection of patient reported symptoms and neurological and physical exams.
  • Severity of adverse events [ Time Frame: Continuously throught the study ]
    This outcome will be assessed by blood, urine and saliva sampling; collection of patient reported symptoms and neurological and physical exams.
 
Raltegravir (Isentress) Pilot Study in Relapsing Multiple Sclerosis
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
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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Relapsing Remitting Multiple Sclerosis
Drug: Raltegravir
400mg twice daily for 3 months
Other Name: Isentress
Experimental: Raltegravir
All eligible patients will complete a 3 months observation period (no medications) followed by 3 months on treatment period. During the treatment period patients will be treated with open label raltegravir 400mg twice daily.
Intervention: Drug: Raltegravir

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
23
September 2014
September 2014   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 55 Years   (Adult)
No
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
 
NCT01767701
008717QM
2012-004847-61 ( EudraCT Number )
Yes
Not Provided
Not Provided
Not Provided
Gavin Giovannoni, Queen Mary University of London
Queen Mary University of London
Merck Sharp & Dohme Corp.
Principal Investigator: Julian Gold, Prof Queen Mary University of London
Principal Investigator: Gavin Giovannoni Queen Mary University of London
Queen Mary University of London
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP