Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment

Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment - a Prospective Observational Study

Multiple Sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS). The symptoms of MS are wide-ranging, but patients perceive loss of physical function (gait) and cognitive function as the most critical consequences of the disease. Moreover, recent studies have shown that already at early disease stages functional impairments are present.

One of the more recent approved medical treatments for MS patients is Alemtuzumab (product name Lemtrada), a humanized monoclonal antibody targeting CD52 cells, that depletes and repopulates B lymphocytes and T lymphocytes, causing sustained changes in the adaptive immunity. In 2013 and 2014 Alemtuzumab was approved in EU and USA, respectively.

With the exception of the MS Functional Composite z-score, the previous clinical studies investigating the effect of Alemtuzumab have exclusively focused on clinical parameters such as MRI indications of disease activity (accumulation of lesion, total and regional brain atrophy etc.), relapse-rates, changes in 'expanded disability status scale' (EDSS) and side-effects/adverse events. However, no previous studies have performed in depth monitoring on how physical or cognitive performance are affected following initiation of treatment with Alemtuzumab despite the paramount importance to patients.

The primary purpose of this project is to monitor the changes in physical performance during the first two years of treatment with Alemtuzumab in a well characterised Danish cohort of people with relapsing-remitting MS. A secondary purpose is to monitor the impact of Alemtuzumab treatment on cognition during the first two years of treatment.

Study Overview

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

• Study Type: Observational
• Enrollment (Actual): 17

Contacts and Locations

• Study Contact: Name: Ulrik Dalgas, MSc,PhD; Phone Number: 45 40123039; Email: dalgas@ph.au.dk
• Study Contact Backup: Name: Lars G Hvid, MSc,PhD; Phone Number: 45 93508717; Email: lhvid@ph.au.dk

Study Locations

• Denmark
  • Jutland
    • Aarhus, Jutland, Denmark, 8000
      • Aarhus University, Health, Section for Sport Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Multiple Sclerosis patients will be recruited from MS clinics all over Denmark.

Description

Inclusion Criteria:

• Clinical definite Multiple Sclerosis diagnosis according to the McDonald criteria
• About to commence alemtuzumab (Lemtrada) treatment
• Expanded Disability Status Scale (EDSS) ≤ 5.5
• Signed informed consent

Exclusion Criteria:

• Co-morbidities that prevent participation in the project (dementia, serious cognitive disorders etc.)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six minute walking test (6MWT)	Change in maximal walking distance covered in 6 minutes	From baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six minute walking test (6MWT)	Change in maximal walking distance covered in 6 minutes	From baseline to 3 months, 6 months, and 12 months
Timed 25 foot walk (T25FWT)	Change in maximal walking speed	From baseline to 3 months, 6 months, 12 months, and 24 months
5 times sit to stand test (5STS)	Change in time to perform 5 times sit to stand test (5STS)	From baseline to 3 months, 6 months, 12 months, and 24 months
Timed Up and Go (TUG)	Change in time to perform Timed Up and Go (TUG)	From baseline to 3 months, 6 months, 12 months, and 24 months
Stair Climbing test	Change in time to perform 9-step stair climbing	From baseline to 3 months, 6 months, 12 months, and 24 months
Six Spot Step Test (SSST)	Change in maximal walking speed while challenging coordination/balance	From baseline to 3 months, 6 months, 12 months, and 24 months
Maximal oxygen uptake (VO2 max)	Change in aerobic power	From baseline to 3 months, 6 months, 12 months, and 24 months
Maximal muscle strength	Change in isometric and dynamic knee extensor muscle strength, isometric hand grip strength	From baseline to 3 months, 6 months, 12 months, and 24 months
Neuromuscular activation	Change in neural drive during maximal isometric knee extension	From baseline to 3 months, 6 months, 12 months, and 24 months
Body composition - limb lean mass	Change in total lower limb lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).	From baseline to 3 months, 6 months, 12 months, and 24 months
Body composition - limb fat mass	Change in total lower limb fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).	From baseline to 3 months, 6 months, 12 months, and 24 months
Body composition - whole body lean mass	Change in total body lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).	From baseline to 3 months, 6 months, 12 months, and 24 months
Body composition - whole body fat mass	Change in total body fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan).	From baseline to 3 months, 6 months, 12 months, and 24 months
Selective Reminding Test (SRT)	Change in cognitive test assessing memory	From baseline to 3 months, 6 months, 12 months, and 24 months
Symbol Digit Modalities Test (SDMT)	Change in cognitive test assessing processing speed	From baseline to 3 months, 6 months, 12 months, and 24 months
Physical activity	Change in accelerometer-based assessment of 24-hour physical activity	From baseline to 3 months, 6 months, 12 months, and 24 months
Clinical Severity of Disease	Estimation of disease severity by the Expanded Disability Severity Scale (EDSS scores: best 0 = normal neurological exam, worst 10 = death due to multiple sclerosis)	From baseline to 3 months, 6 months, 12 months, and 24 months
Relapse frequency	Number of relapses	From baseline to 3 months, 6 months, 12 months, and 24 months
12-item Multiple Sclerosis Walking Scale (MSWS-12)	Self-reported questionnaire assessing impact of MS on walking ability (MSWS-12 scores: best 0, worst 100)	From baseline to 3 months, 6 months, 12 months, and 24 months
Modified Fatigue Impact Scale (MFIS)	Self-reported questionnaire assessing impact of MS-induced fatigue on a persons life (MFIS total scores: best 0, worst 84; physical subscale scores: best 0, worst 36; cognitive subscale scores: best 0, worst 40; psychosocial subscale scores: best 0, worst 8)	From baseline to 3 months, 6 months, 12 months, and 24 months
Multiple Sclerosis Impact Scale (MSIS-29)	Self-reported questionnaire assessing impact of MS on day-to-day life, from a physical perspective (MSIS-29 physical scale: best 0, worst 100 (greater impact of disease on daily function = worse health) and from a psychological perspective (MSIS-29 psychological scale: best 0, worst 100 (greater impact of disease on daily function = worse health)	From baseline to 3 months, 6 months, 12 months, and 24 months
Hospital Anxiety and Depression Scale (HADS)	Self-reported questionnaire assessing impact of MS on anxiety (scores: best 0, worst 21) and depression (scores: best 0, worst 21)	From baseline to 3 months, 6 months, 12 months, and 24 months

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Ulrik Dalgas, MSc,PhD, Aarhus University, Health, Section for Sport Science

Publications and helpful links

General Publications

• Hvid LG, Stenager E, Dalgas U. Objectively assessed physiological, physical, and cognitive function along with patient-reported outcomes during the first 2 years of Alemtuzumab treatment in multiple sclerosis: a prospective observational study. J Neurol. 2022 Sep;269(9):4895-4908. doi: 10.1007/s00415-022-11134-7. Epub 2022 Apr 28.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): July 30, 2020
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: January 9, 2019
• First Submitted That Met QC Criteria: January 15, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Estimated): September 6, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Antineoplastic Agents; Antineoplastic Agents, Immunological; Alemtuzumab
• Other Study ID Numbers: MS_Improve

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No