Clinical trial NCT03873389: Ocrelizumab Effects on the Metabolome in MS
Official title: Evaluating the Effects of Ocrelizumab on the Circulating Metabolome in Multiple Sclerosis (MS)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2019-03-13
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants will be patients diagnosed with relapsing remitting multiple sclerosis between 18 and 75 years of age who are being started on ocrelizumab by the treating neurologist, are willing to return for visits every six months and do not have any other neurological disorder or significant metabolic comorbidity.

Brief summary: In this observational study, the investigators aim to recruit 50 patients over an 10-12 month period. The investigators will recruit patients with relapsing-remitting MS (based on 2017 McDonald Criteria) beginning treatment with ocrelizumab and fulfilling study inclusion and exclusion criteria. Participants recruited in this study will be participants in the Johns Hopkins MS Precision Medicine Center of Excellence bio-banking protocol which requires collection of serum and plasma at 6-monthly intervals and hence will have blood collection performed prior to Ocrevus start and then at 6, 12, 18 and 24 months following ocrelizumab initiation as part of the bio-banking protocol. All recruited participants will provide written informed consent.

The investigators will collect demographic and clinical characteristics at baseline and update these at follow-up visits. These will include disease duration, co-morbidities, relapses, treatment status and history. The investigators will also collect physiological variables - height and weight at each visit.

All recruited patients will return for follow up visits at 6,12, 18 and 24 months post-ocrelizumab initiation. At each visit patients will undergo the following evaluations - EDSS, MSFC, SDMT, fatigue scale (MFIS), quality of life measure (MS-QOL), depression scale (Beck depression inventory, 2nd version) and Block Food Frequency Questionnaire.

The investigators will then utilize plasma collected at the various time points to perform global metabolomics analysis. This will yield measures of various metabolites in the circulation, including amino acids and metabolites of the amino acids. The investigators will utilize this data to determine the change in the circulating metabolome produced by treatment with ocrelizumab.

Following this the investigators will assess changes in the various clinical measures collected - disability (EDSS, MSFC), cognition (SDMT), mood (BDI-II), fatigue (MFIS) and quality of life (MS-QOL) with Ocrelizumab treatment and correlate these with the changes noted in the metabolome. This approach will allow us to determine whether the metabolic changes are associated with/ could underlie the changes noted in clinical measures.


Eligibility criteria: Inclusion Criteria:

* Between 18-75 years of age
* Diagnosis of relapsing remitting multiple sclerosis (RRMS) based on 2017 McDonald Criteria
* Initiating treatment with Ocrelizumab based on decision of the treating physician
* Able to return for visits every 6 months to Johns Hopkins MS Center

Exclusion Criteria:

* Presence of additional neuroinflammatory or neurodegenerative disorder
* Steroids within the past 30 days
* Other significant metabolic comorbidity - eg: uncontrolled hypothyroidism or diabetes
* Likely to switch therapy in the following year
* Previous treatment with rituximab or other chemotherapy agents

Primary outcomes:
measure: Change in Global metabolomic profile
timeFrame: Baseline to 24 months
Secondary outcomes:
measure: Change in Expanded Disability Status Scale
timeFrame: Baseline to 24 months
measure: Change in Multiple Sclerosis Functional Composite score
timeFrame: Baseline to 24 months
measure: Change in Modified Fatigue Impact Scale score
timeFrame: Baseline to 24 months
measure: Change in Multiple Sclerosis Quality of Life score
timeFrame: Baseline to 24 months.
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Pavan Bhargava, MBBS, MD
role: PRINCIPAL_INVESTIGATOR
References: