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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03806387
• Other study ID #: MS_Improve
• Status: Completed
• Start date: March 1, 2017
• Est. completion date: June 30, 2021

Study information

• Verified date: March 2021
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 30, 2021
• Est. primary completion date: July 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.)

Related Conditions & MeSH terms

• Multiple Sclerosis

Intervention

Drug:
• Alemtuzumab
Alemtuzumab will be given two times, separated by 1 year.

Locations

Country	Name	City	State
Denmark	Aarhus University, Health, Section for Sport Science	Aarhus	Jutland

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Genzyme, a Sanofi Company

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Six minute walking test (6MWT)	Change in maximal walking distance covered in 6 minutes	From baseline to 24 months
Secondary	Six minute walking test (6MWT)	Change in maximal walking distance covered in 6 minutes	From baseline to 3 months, 6 months, and 12 months
Secondary	Timed 25 foot walk (T25FWT)	Change in maximal walking speed	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	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
Secondary	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
Secondary	Stair Climbing test	Change in time to perform 9-step stair climbing	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	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
Secondary	Maximal oxygen uptake (VO2 max)	Change in aerobic power	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	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
Secondary	Neuromuscular activation	Change in neural drive during maximal isometric knee extension	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Selective Reminding Test (SRT)	Change in cognitive test assessing memory	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	Symbol Digit Modalities Test (SDMT)	Change in cognitive test assessing processing speed	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	Physical activity	Change in accelerometer-based assessment of 24-hour physical activity	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	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
Secondary	Relapse frequency	Number of relapses	From baseline to 3 months, 6 months, 12 months, and 24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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