PRC-REMS: Patient Research Cohort: Rapidly Evolving Multiple Sclerosis

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT01044576
• Collaborator: Medical Research Council (Other), Imperial College Healthcare NHS Trust (Other), University College, London (Other), Queen Mary University of London (Other), GlaxoSmithKline (Industry), University of Cambridge (Other)
• Enrollment: 200
• Location: 1
• Actual Duration (Months): 34
• Patients Per Site Per Month: 5.9

Study Details

Study Description

Brief Summary

The primary goal of the research cohort is to facilitate patient access to clinical trials testing new therapeutic interventions, or access to second- line treatments.

Secondary objectives of the research cohort study are to obtain detailed clinical phenotyping and immunological analysis of blood samples, aiming to identify and validate biomarkers of disease activity and response to treatment and prognostic markers.

Condition or Disease	Intervention/Treatment	Phase
Relapsing-remitting Multiple Sclerosis; Secondary Progressive Multiple Sclerosis

Study Design

• Study Type: Observational
• Actual Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Patient Research Cohort: Rapidly Evolving Multiple Sclerosis Opening the Window of Therapeutic Opportunity
• Actual Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Nov 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Multiple Sclerosis Patients with relapsing-remitting or secondary progressive multiple sclerosis

Outcome Measures

Primary Outcome Measures

1. Proportion of Research Cohort Subjects Referred Into a Clinical Trial or Offered Treatment With an Appropriate Second-line Therapy. [Two years]

   The primary goal of the observational research cohort is to facilitate patient access to clinical trials testing new therapeutic interventions or appropriate management for rapidly evolving multiple sclerosis (MS). This was devised as a single, combined primary outcome measure. The primary outcome is the proportion of research cohort subjects either referred into a clinical trial or offered treatment with an appropriate second-line therapy. (approved Protocol Version 4.1 - September 13th, 2011). The statistical assumption based on data from similar research cohorts stipulated that 50% of recruited patients will consent to proceed to further clinical trials or access new therapies.

Secondary Outcome Measures

1. Access and Utilization of Cohort Data [two years]

   The outcome reports the Number of participants whose data was used in any approved research. Examples of utilisation of data include imaging data analysis for MS-related research performed on the study participants' dataset and analysis of correlation of clinical phenotype with imaging data. Given the exploratory nature, no specific quantitative assumptions are made on the secondary outcome. Examples of studies utilising the anonymised cohort data: (1) Rapidly evolving multiple sclerosis: MRI findings predict clinical progression and disease phenotype (Dr Jean Lee, Dr A Waldmann, Dr R Newbould, ICL). (2) A study to characterize the novel TSPO PET radioligand [18F]PBR111 as an in vivo marker of microglial activation in Multiple Sclerosis (Dr A Colasanti, Imanova Ltd and GlaxoSmithKline). Conditions for participants to meet this outcome measure are: (A) completion of study visits (B) maintained (non-revoked) consent and (C) utilisation of the anonymised data in any further study.

2. Development of Biomarkers [two years]

   The outcome consists of the Number of participants whose data was used in biomarkers development studies. Biomarkers studies include analysis of blood immunological studies performed on the study participants' dataset and analysis of correlation of clinical phenotype with immunological data, examples given below. Conditions for participants to meet this outcome measure are: (A) completion of study visits (B) maintained (non-revoked) consent and (C) utilisation of the anonymised immunological and clinical data in any biomarkers study. Given the exploratory nature, no quantitative assumptions are made on the outcome. Examples of studies of biomarkers: 1) Functional relevance of haematopoietic stem cell mobilisation following therapeutic alpha 4-integrin blockade in multiple sclerosis (Dr MMattoscio, ICL). 2)The relationship between T cell responses and disease progression in demyelinating disorders of the central nervous system (Prof D Altmann, ICL).

3. Development of Clinical Prognostic Markers. [two years]

   The outcome consists of the Number of participants whose data was used in studies aimed at the development of markers of clinical prognosis. Those are studies involving statistical analysis and models that may enable prognostic predictions from clinical phenotype, imaging and immunological data in any combination, with examples indicated below. Conditions for participants to meet this outcome measure are: (A) completion of study visits (B) maintained (non-revoked) consent and (C) utilisation of the anonymised imaging immunological and clinical data in any prognostic development research. Given their exploratory nature, no specific quantitative assumptions are made on the secondary outcome. Example of studies of prognostic markers: 1) Worse Physical Disability is associated with High Blood frequency of CD8+CD57+(ILT2+PD-1+) T-cells in MS Patients with Older Appearing Brains (Dr S Jacobs, Prof R Nicholas and Prof J Cole, Imperial College London and KCL).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• Male or Female, aged 18-65

• Able to give informed consent

• Diagnosis of MS according to to the revised McDonald's criteria (Polman et al. Ann Neurol 2005)

• Relapsing-remitting or secondary progressive MS form

• Disease duration ≤15 years from diagnosis

• Expanded disability status scale (EDSS) score 2.0 to 6.0 at screening evaluation

• Highly active and/or treatment-refractory MS activity defined as:

1. Two or more clinical exacerbations in the previous 12 months, regardless of treatment; OR:

2. One clinical exacerbation and sustained increase in EDSS of at least 1 point in the previous 12 months after receiving immune-modifying treatment, OR:

3. Evidence of gadolinium (contrast)-enhancement or increase of T2 lesion load at MRI after receiving immune-modifying treatment. OR

4. Not tolerating or not wishing to receive any of the available immune-modifying treatments and meeting one of the stated criteria (b or c) for MS activity in treated subjects (1 relapse and increase in EDSS of at least 1 point in the previous 12 months; or evidence of contrast-enhancement or increase of T2 lesion load at MRI).

Exclusion Criteria:

• Contraindication to MRI including but not limited to intracranial aneurism clips (except Sugita), history of intra-orbital metal fragments that have not been removed by an MD (as confirmed by orbital X-Ray), pacemaker and non-MR compatible heart valves, inner ear implants, history of claustrophobia or subject feels unable to lie still on their back for a period of 1.5 hours in the MRI scanner.

• If female, positive urine pregnancy test

• History or presence of renal impairment (e.g. serum creatinine clearance less than 30ml/min)

• Inability to give informed consent/comply with study procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Imperial College NHS Trust	London		United Kingdom

Sponsors and Collaborators

• Imperial College London
• Medical Research Council
• Imperial College Healthcare NHS Trust
• University College, London
• Queen Mary University of London
• GlaxoSmithKline
• University of Cambridge

Investigators

• Principal Investigator: Paolo A Muraro, MD, Imperial College London

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT01044576
• Other Study ID Numbers: CRO1387; G0800679
• First Posted: Jan 8, 2010
• Last Update Posted: Mar 8, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: Multiple Sclerosis
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Sclerosis

Study Results

Participant Flow

Arm/Group Title	Multiple Sclerosis
Arm/Group Description	Patients with relapsing-remitting or secondary progressive multiple sclerosis
Period Title: Overall Study
STARTED	200
COMPLETED	200
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Multiple Sclerosis
Arm/Group Description	Patients with relapsing-remitting or secondary progressive multiple sclerosis
Overall Participants	200
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	200 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (8)
Sex: Female, Male (Count of Participants)
Female	151 75.5%
Male	49 24.5%
Region of Enrollment (participants) [Number]
United Kingdom	200 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Research Cohort Subjects Referred Into a Clinical Trial or Offered Treatment With an Appropriate Second-line Therapy.
Description	The primary goal of the observational research cohort is to facilitate patient access to clinical trials testing new therapeutic interventions or appropriate management for rapidly evolving multiple sclerosis (MS). This was devised as a single, combined primary outcome measure. The primary outcome is the proportion of research cohort subjects either referred into a clinical trial or offered treatment with an appropriate second-line therapy. (approved Protocol Version 4.1 - September 13th, 2011). The statistical assumption based on data from similar research cohorts stipulated that 50% of recruited patients will consent to proceed to further clinical trials or access new therapies.
Time Frame	Two years

Outcome Measure Data

Analysis Population Description

Inclusion criteria were aimed to selecting a patient population who is at increased risk of continued progression and loss of function but has not accumulated irreversible neuronal injury or degeneration. All subjects who consented, met the study inclusion criteria and completed the study were included in this outcome analysis. There was no pre-planned subgroup analysis.

Arm/Group Title	Multiple Sclerosis
Arm/Group Description	Patients with relapsing-remitting or secondary progressive multiple sclerosis
Measure Participants	200
Count of Participants [Participants]	178 89%

2. Secondary Outcome

Title	Access and Utilization of Cohort Data
Description	The outcome reports the Number of participants whose data was used in any approved research. Examples of utilisation of data include imaging data analysis for MS-related research performed on the study participants' dataset and analysis of correlation of clinical phenotype with imaging data. Given the exploratory nature, no specific quantitative assumptions are made on the secondary outcome. Examples of studies utilising the anonymised cohort data: (1) Rapidly evolving multiple sclerosis: MRI findings predict clinical progression and disease phenotype (Dr Jean Lee, Dr A Waldmann, Dr R Newbould, ICL). (2) A study to characterize the novel TSPO PET radioligand [18F]PBR111 as an in vivo marker of microglial activation in Multiple Sclerosis (Dr A Colasanti, Imanova Ltd and GlaxoSmithKline). Conditions for participants to meet this outcome measure are: (A) completion of study visits (B) maintained (non-revoked) consent and (C) utilisation of the anonymised data in any further study.
Time Frame	two years

Outcome Measure Data

Analysis Population Description

Inclusion criteria were aimed to selecting a patient population who is at increased risk of continued progression and loss of function but has not accumulated irreversible neuronal injury or degeneration. All subjects who consented, met the study inclusion criteria and completed the study were included in this outcome analysis. There was no pre-planned subgroup analysis.

Arm/Group Title	Multiple Sclerosis
Arm/Group Description	Patients with relapsing-remitting or secondary progressive multiple sclerosis
Measure Participants	200
Count of Participants [Participants]	179 89.5%

3. Secondary Outcome

Title	Development of Biomarkers
Description	The outcome consists of the Number of participants whose data was used in biomarkers development studies. Biomarkers studies include analysis of blood immunological studies performed on the study participants' dataset and analysis of correlation of clinical phenotype with immunological data, examples given below. Conditions for participants to meet this outcome measure are: (A) completion of study visits (B) maintained (non-revoked) consent and (C) utilisation of the anonymised immunological and clinical data in any biomarkers study. Given the exploratory nature, no quantitative assumptions are made on the outcome. Examples of studies of biomarkers: 1) Functional relevance of haematopoietic stem cell mobilisation following therapeutic alpha 4-integrin blockade in multiple sclerosis (Dr MMattoscio, ICL). 2)The relationship between T cell responses and disease progression in demyelinating disorders of the central nervous system (Prof D Altmann, ICL).
Time Frame	two years

Outcome Measure Data

Analysis Population Description

Inclusion criteria were aimed to selecting a patient population who is at increased risk of continued progression and loss of function but has not accumulated irreversible neuronal injury or degeneration. All subjects who consented, met the study inclusion criteria and completed the study were included in this outcome analysis. There was no pre-planned subgroup analysis.

Arm/Group Title	Multiple Sclerosis
Arm/Group Description	Patients with relapsing-remitting or secondary progressive multiple sclerosis
Measure Participants	200
Count of Participants [Participants]	179 89.5%

4. Secondary Outcome

Title	Development of Clinical Prognostic Markers.
Description	The outcome consists of the Number of participants whose data was used in studies aimed at the development of markers of clinical prognosis. Those are studies involving statistical analysis and models that may enable prognostic predictions from clinical phenotype, imaging and immunological data in any combination, with examples indicated below. Conditions for participants to meet this outcome measure are: (A) completion of study visits (B) maintained (non-revoked) consent and (C) utilisation of the anonymised imaging immunological and clinical data in any prognostic development research. Given their exploratory nature, no specific quantitative assumptions are made on the secondary outcome. Example of studies of prognostic markers: 1) Worse Physical Disability is associated with High Blood frequency of CD8+CD57+(ILT2+PD-1+) T-cells in MS Patients with Older Appearing Brains (Dr S Jacobs, Prof R Nicholas and Prof J Cole, Imperial College London and KCL).
Time Frame	two years

Outcome Measure Data

Analysis Population Description

Inclusion criteria were aimed to selecting a patient population who is at increased risk of continued progression and loss of function but has not accumulated irreversible neuronal injury or degeneration. All subjects who consented, met the study inclusion criteria and completed the study were included in this outcome analysis. There was no pre-planned subgroup analysis.

Arm/Group Title	Multiple Sclerosis
Arm/Group Description	Patients with relapsing-remitting or secondary progressive multiple sclerosis
Measure Participants	200
Count of Participants [Participants]	179 89.5%

Adverse Events

Time Frame	2 years
Arm/Group Title	Multiple Sclerosis
Arm/Group Description	Patients with relapsing-remitting or secondary progressive multiple sclerosis
All Cause Mortality
	Multiple Sclerosis
	Affected / at Risk (%)	# Events
Total	0/200 (0%)
Serious Adverse Events
	Multiple Sclerosis
	Affected / at Risk (%)	# Events
Total	0/200 (0%)
Other (Not Including Serious) Adverse Events
	Multiple Sclerosis
	Affected / at Risk (%)	# Events
Total	0/200 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.