Ocrelizumab Effects on the Metabolome in MS

Evaluating the Effects of Ocrelizumab on the Circulating Metabolome in Multiple Sclerosis (MS)

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Ocrelizumab

• Study Type: Observational
• Enrollment (Actual): 25

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ocrelizumab; All participants enrolled in the study. All participants will be receiving the treatment of interest (Ocrelizumab)	Drug: Ocrelizumab; Patients who are beginning this medication based on patient's treating physician's recommendation will be enrolled in the study.; Other Names: Ocrevus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Global metabolomic profile	Change in relative abundance of various metabolites, including amino acids and metabolites of the amino acids, in plasma measured using mass spectrometry	Baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Expanded Disability Status Scale	Change in level of disability as measured by a structured neurological examination resulting in the participants being rated on a scale from 1-10. Higher scores reflect greater physical disability.	Baseline to 24 months
Change in Multiple Sclerosis Functional Composite score	Change in the multiple sclerosis functional composite which consists of three assessments of walking speed, processing speed and finger dexterity. The scores are combined to provide a Z-score (number of standard deviations away from mean of a normal population) with lower scores representing greater abnormality.	Baseline to 24 months
Change in Modified Fatigue Impact Scale score	Change in scores on the modified fatigue impact scale which has 21 questions regarding the impact of fatigue on daily activities and scores range from 0-84. Higher scores reflect greater impact of fatigue on functioning.	Baseline to 24 months
Change in Multiple Sclerosis Quality of Life score	Change in physical and mental health scores as assessed using the Multiple Sclerosis Quality of Life-54 (MSQOL-54) instrument. This 54-item instrument generates 12 subscales along with two summary scores, and two additional single-item measures. Two summary scores - physical health and mental health - are derived from a weighted combination of scale scores. Higher scores suggest a better quality of life.	Baseline to 24 months.

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Pavan Bhargava, MBBS, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2019
• Primary Completion (Actual): June 22, 2023
• Study Completion (Actual): December 5, 2023

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: IRB00205181

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No