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Effect of Physical ACtivity in Fingolimod Treated patiEnts (PACE) With Relapsing-remitting Multiple Sclerosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01490840
First received: December 9, 2011
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

This study will evaluate the effect of an individualized web-based physical training in fingolimod -treated patients.


Condition Intervention Phase
Fatigue in Multiple Sclerosis
Drug: Physical exercise
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 6-month, Multicenter, Randomized, Controlled Parallel Group Study to Evaluate the Effect of Physical Training on Fatigue in Patients With Relapsing-remitting Multiple Sclerosis Treated With Fingolimod, Followed by a 6 Month Optional Extension Phase

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in fatigue from baseline to 6 month and 12 months as measured by the Modified Fatigue Impact Scale (mFIS ). [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    The mFIS provides an assessment of the effects of fatigue in terms of physical, cognitive, and psychosocial functioning. It is a 21-item, structured, self-report questionnaire that generally can be completed with little or no intervention from an interviewer. The mFIS will be performed at - screening, baseline, week 13, week 26, week 35 and week 53


Secondary Outcome Measures:
  • Change in isomentric and dynamic muscular strength as measured by changes in knee and trunk flexion and tension by Isomed 2000 isometric measurement device [ Time Frame: From baseline to 6 months and 12 months ] [ Designated as safety issue: No ]

    Isometric and dynamic muscular strength measured by Isomed 2000 isometric measurement device (knee flexion/tension, trunk flexion/extension) and sit-to-stand-test.

    Isomed 2000 device measures muscular flexion and tension under standardized training conditions.

    The Sit to Stand Test is a functional outcome measure of the lower-extremity muscle power. The test will be performed 3 times with one minute rest in between, the best attempt out of three is used for the analysis.


  • Change in quality of life from baseline to 6 and 12 months as measured by the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: No ]
    The Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS) consists of 38 items, 28 of which are the basis for computation of five subscale scores reflecting major dimensions of health-related quality of life (HRQoL) in MS: Fatigue/Thinking (4 items), Mobility lower limb (5 items), Mobility upper limb (5 items), Social function (6 items) and Mood (eight items). Internal consistency, retest reliability and validity of the HAQUAMS are not affected by cognitive impairment in MS

  • Change in fatigue from baseline to 6 and 12 months as measured by the WEIMuS (Würzburg Fatigue Inventory for MS) [ Time Frame: Baseline to 6 months and 12 months ] [ Designated as safety issue: No ]
    The WEIMuS (Würzburg Fatigue Inventory for MS) scale is a validated self-assessment instrument to quantify the degree of fatigue. The scale consists of 17 items with 5 categories that are scored from '0' to '4', with the total sum score ranging from 0 to 68; higher scores indicate higher degrees of fatigue. Subscores for cognitive and physical fatigue are ranging from 0 to 36 and from 0 to 32, respectively.

  • Change in depression from baseline to 6 and 12 months as measured by the Beck Depression Inventory Second Edition (BDI-II) [ Time Frame: Baseline to 6 months and 12 months ] [ Designated as safety issue: No ]
    The Beck Depression Inventory Second Edition (BDI-II) is a 21-item self-report instrument intended to assess the existence and severity of symptoms of depression as listed in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders Fourth Edition. Scoring: Each of the 21 items corresponding to a symptom of depression is summed to give a single score for the BDI-II. There is a four-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.

  • Change in aerobic capacity from baseline to 6 and 12 months as measured by a physical endurance spiroergometry on a treadmill [ Time Frame: Baseline to 6 and 12 months ] [ Designated as safety issue: No ]
    Physical endurance spiroergometry will be accomplished. Ergometry will be assessed according to national guidelines of the German society for sports medicine. Ergometry is a combined examination of circulation and lung function and will be performed as a submaximal or maximal test depending on the patient´s individual performance


Enrollment: 178
Study Start Date: November 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exercise for 6 months
Fingolimod as baseline immunomodulatory multiple sclerosis treatment is prescribed as per clinical practice. Patients will have a baseline physical assessment before randomisation to study arms (V1a) After baseline (V2) visit, patients from the training group visit an introductory group session, hosted by a sports therapist. The individual training schedule is comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants document each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis is allowed for treatment of relapses as clinically warranted. Steroid treatment should consist of 3-5 days and up to 1,000 mg methylprednisolone/day.
Drug: Physical exercise
Strength training exercises are performed against own body weight or with training aids like elastic rubber bands or gymballs. All exercises are home-based. To increase balance and core stability, a subset of exercises is performed on shaky ground and/or one-legged. Exercise intensity, duration and frequency are individually assigned by a sports therapist. For each muscle group, a set of exercises of increasing difficulty allows for individual and progressive training adaption. Therapists can choose from an exercise database of approximately 150 different strength exercises with different graduation.
Experimental: Waiting group for 6 months, followed by Exercise for 6 months
Fingolimod as baseline immunomodulatory multiple sclerosis treatment is prescribed as per clinical practice. After a 6 months waiting period, during 26th week (V6) visit, patients from the waiting group visit an introductory group session, hosted by a sports therapist. The individual training schedule is comprised of strength exercises twice a week for 30-45 minutes and endurance training once a week for 20-60 minutes for 6 months. The participants document each training session thoroughly via the web-based application (duration, type of exercises, number of repetitions and sets, perceived exertion). A standard course of corticosteroids (methylprednisolone) on an inpatient or outpatient basis is allowed for treatment of relapses as clinically warranted. Steroid treatment should consist of 3-5 days and up to 1,000 mg methylprednisolone/day.
Drug: Physical exercise
Strength training exercises are performed against own body weight or with training aids like elastic rubber bands or gymballs. All exercises are home-based. To increase balance and core stability, a subset of exercises is performed on shaky ground and/or one-legged. Exercise intensity, duration and frequency are individually assigned by a sports therapist. For each muscle group, a set of exercises of increasing difficulty allows for individual and progressive training adaption. Therapists can choose from an exercise database of approximately 150 different strength exercises with different graduation.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria
  • Patients with Expanded Disability Status Scale (EDSS) score of 0-3.5 (including)
  • Immunomodulatory treatment with prescribed fingolimod for at least one month prior to baseline
  • Fatigue score assessed by mFIS of equal or greater than 14 at screening
  • Neurologically stable with no evidence of relapse within 30 days prior to inclusion date

Exclusion Criteria:

  • Patients who have been treated with:

    • systemic corticosteroids or immunoglobulins within 1 month prior to randomization;
    • immunosuppressive medications such as azathioprine, cyclophosphamide, or methotrexate within 3 months prior to randomization;
    • monoclonal antibodies (including natalizumab) within 3 months prior to randomization;
    • mitoxantrone within 6 months prior to randomization
    • cladribine at any time.
  • Patients with any medically unstable condition, as assessed by the primary treating physician at each site.
  • Patients with any of the following cardiovascular conditions :

    • history of cardiac arrest;
    • history of myocardial infarction or with current unstable ischemic heart disease;
    • history of angina pectoris due to coronary spasm or history of Raynaud syndrome
    • Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the investigator;
    • history or presence of a second-degree AV block, Type II or a third-degree AV
    • block
    • patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or
    • III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide,
    • dofelitide);
    • proven history of sick sinus syndrome or sino-atrial heart block;
    • uncontrolled hypertension
  • Clinically relevant internal disease (e.g. uncorrected anemia) or orthopedic diseases (e.g. scoliosis) that might interfere with physical training
  • Any severe disability or clinical impairment that can prevent the patient to meet all study requirements at the investigator`s discretion

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01490840

Locations
Germany
Novartis Investigative Site
Aachen, Germany, 52062
Novartis Investigative Site
Alzenau, Germany, 63755
Novartis Investigative Site
Aschaffenburg, Germany, 63739
Novartis Investigative Site
Bad Mergentheim, Germany, 97980
Novartis Investigative Site
Bamberg, Germany, 96052
Novartis Investigative Site
Bayreuth, Germany, 95445
Novartis Investigative Site
Berlin, Germany, 10691
Novartis Investigative Site
Berlin, Germany, 10625
Novartis Investigative Site
Berlin, Germany, 10437
Novartis Investigative Site
Berlin, Germany, 12587
Novartis Investigative Site
Berlin, Germany, 13347
Novartis Investigative Site
Bielefeld, Germany, 33647
Novartis Investigative Site
Bochum, Germany, 44787
Novartis Investigative Site
Böblingen, Germany, 71032
Novartis Investigative Site
Dortmund, Germany, 44135
Novartis Investigative Site
Erbach, Germany, 64711
Novartis Investigative Site
Erlangen, Germany, 91054
Novartis Investigative Site
Frankfurt, Germany, 65929
Novartis Investigative Site
Hamburg, Germany, 22179
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Jena, Germany, 07740
Novartis Investigative Site
Kassel, Germany, 34121
Novartis Investigative Site
Leipzig, Germany, 04299
Novartis Investigative Site
Potsdam, Germany, 14471
Novartis Investigative Site
Prien, Germany, 83209
Novartis Investigative Site
Regensburg, Germany, 93053
Novartis Investigative Site
Siegen, Germany, 57076
Novartis Investigative Site
Sinsheim, Germany, 74889
Novartis Investigative Site
Stuttgart, Germany, 70191
Novartis Investigative Site
Stuttgart, Germany, 70178
Novartis Investigative Site
Teupitz, Germany, 15755
Novartis Investigative Site
Unterhaching, Germany, 82008
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01490840     History of Changes
Other Study ID Numbers: CFTY720DDE07, 2011-002969-38
Study First Received: December 9, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration
Germany: Ministry of Health

Keywords provided by Novartis:
Fatigue
MS
Multiple Sclerosis
Exercise
Physical activity
Physical training
Fingolimod

Additional relevant MeSH terms:
Fatigue
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Signs and Symptoms
Fingolimod
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014