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Trial record 2 of 6 for:    "chronic fatigue syndrome" AND "Saline"

B-lymphocyte Depletion Using Rituximab in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME). A Randomized Phase-III Study. (RituxME)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
The Research Council of Norway
Norwegian Department of Health and Social Affairs
The Kavli Foundation
Oslo University Hospital
St. Olavs Hospital
University Hospital of North Norway
Sykehuset Telemark
MEandYou Foundation
The Norwegian ME association
Information provided by (Responsible Party):
Haukeland University Hospital
ClinicalTrials.gov Identifier:
NCT02229942
First received: August 29, 2014
Last updated: April 11, 2016
Last verified: April 2016
  Purpose
The hypothesis is that a subgroup of patients with Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) have a chronically activated immune system and may benefit from B-lymphocyte treatment using the monoclonal anti-CD20 antibody rituximab with induction and maintenance treatment.

Condition Intervention Phase
Chronic Fatigue Syndrome/ Myalgic Encephalitis (CFS/ME)
Drug: Rituximab
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: B-lymphocyte Depletion Using the Monoclonal Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME). A Multicentre, Randomized, Double-blind and Placebo Controlled Phase-III Study With Rituximab Induction and Maintenance Treatment.

Resource links provided by NLM:


Further study details as provided by Haukeland University Hospital:

Primary Outcome Measures:
  • Fatigue score, selfreported. [ Time Frame: Course of Fatigue score during 24 months follow-up. ] [ Designated as safety issue: No ]

    Selfreported Fatigue score is registered every second week, as the mean score for the four symptoms: "Post-exertional malaise", "Fatigue", "Need for rest", "Daily functioning" (scale 0-6). Mean Fatigue scores for the time intervals 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 months are recorded for each patient. These data are used for statistical analysis. The difference in course of Fatigue score during 24 months follow-up, between the rituximab and placebo groups, will constitute the primary endpoint.

    Overall response is recorded as the effect on CFS/ME symptoms during 24 months follow-up. The overall response is not predefined to a specific time interval, but is defined as mean Fatigue score at least 4.5 for at least 8 consecutive weeks for moderate response, and mean Fatigue score at least 5.0 for at least 8 consecutive weeks for major response. Single response periods and the sum of response periods during 24 months follow-up will be recorded.



Secondary Outcome Measures:
  • Short Form-36 (SF-36) [ Time Frame: Changes in SF-36 scores during 24 months follow-up ] [ Designated as safety issue: No ]

    SF-36 (ver 1.2) are selfreported by patients at baseline, and at 3, 6, 9, 12, 15, 18, 21 and 24 months follow-up. Changes in Physical health summary score, Physical function, and "Mean of five subdimensions" (Physical function, Bodily pain, Vitality, Social function, General health) are recorded. The difference in course during 24 months follow-up, between the rituximab and placebo groups, will constitute secondary endpoints.

    Also, the difference between rituximab and placebo groups, in changes from baseline to recording at 18 months, for Physical health summary score, Physical function, and "mean of five SF-36 subdimensions", constitute secondary endpoints.


  • Physical activity (Sensewear armband) [ Time Frame: Analyzed at baseline and at interval 17-21 months ] [ Designated as safety issue: No ]
    The patients' physical activity level, in a home setting for 7 consecutive days, is recorded using Sensewear armbands, with registration at baseline and repeated in the time interval 17-21 months follow-up. Changes from baseline to analysis during the time interval 17-21 months, for mean number of steps per 24h, maximum number of steps per 24h, mean duration per 24h with activity level at least 3.5 METs, max duration per 24h with activity level at least 3.5 METs, are recorded. The difference between rituximab and placebo groups will constitute secondary endpoints.

  • Self-recorded "Function level" [ Time Frame: Course during 24 months follow-up ] [ Designated as safety issue: No ]

    Self-recorded "Function level" (scale 0-100, compared to healthy state, according to a set of examples) are registered every second week. Mean "Function level" for the time intervals 0-4, 4-8, 8-12, 12-16, 16-20, 20-24 months are calculated. The difference in course of "Function level", between the rituximab and placebo groups, constitute a secondary endpoint.

    Also, the differences between the rituximab and placebo groups, for changes in selfreported "Fatigue score" and in selfreported "Function level", calculated from baseline to the mean value during the time interval 16-20 months, constitute secondary endpoints.


  • Fatigue Severity Scale [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Fatigue Severity Scale (FSS) is self-recorded at baseline and at 6, 12, 18, 24 months. The difference between the rituximab and placebo groups, in changes in FSS from baseline to 18 months follow-up, constitutes a secondary endpoint.

  • Clinical response duration [ Time Frame: During 24 months follow-up ] [ Designated as safety issue: No ]

    Clinical response periods, defined as consecutive self-recorded Fatigue score at least 4.5 (scale 0-6) for a minimum of 8 weeks, during 24 months follow-up, are recorded.

    The difference in the longest consecutive clinical response period, between rituximab and placebo groups, constitutes a secondary endpoint.


  • Sustained clinical response at 24 months [ Time Frame: Assessment at 24 months ] [ Designated as safety issue: No ]
    The difference between rituximab and placebo groups, in fraction of patients with sustained clinical response (defined as Fatigue score of at least 4.5) at 24 months, constitute a secondary endpoint.


Other Outcome Measures:
  • Toxicity and side-effects [ Time Frame: During 24 months follow-up ] [ Designated as safety issue: Yes ]
    Toxicity and side effects will be recorded throughout 24 months follow-up, as specified in the protocol.


Estimated Enrollment: 152
Study Start Date: September 2014
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab
Rituximab induction (two infusions two weeks apart) and maintenance (infusions at 3, 6, 9 and 12 months)
Drug: Rituximab

Induction with two infusions two weeks apart, rituximab 500 mg/m2 (max 1000 mg).

Maintenance with rituximab infusions (500 mg fixed dose) at 3, 6, 9 and 12 months.

Other Names:
  • Rituxan
  • Mabthera
Placebo Comparator: Placebo
Saline (with added albumin), two infusions two weeks apart, followed by infusions at 3, 6, 9 and 12 months.
Drug: Placebo
Saline (NaCl 0,9%) added human albumin (Flexbumin) 0,4 mg/ml, two infusions two weeks apart. Maintenance infusions after 3,6, 9 and 12 months.
Other Name: Saline

Detailed Description:

We have published a case series of pilot patient observations with B-cell depletion in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) (Fluge and Mella, BMC Neurol, 2009). Subsequently, we published a small randomized and double-blind phase II study using rituximab induction two infusions two weeks apart (Fluge et al, Plos One, 2011).

We have completed an open label phase II study with 29 patients using rituximab induction and maintenance treatment (six rituximab infusions over 15 months, with follow-up for three years, unpublished).

We hypothesize that a subgroup of patients with Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) have a chronically activated immune system involving B-lymphocytes, possibly a variant of an autoimmune disease, and that patients may benefit from B-cell depletion therapy.

Three substudies will be performed:

Endothelial function: assessment of Flow-Mediated Dilation and skin microcirculation at baseline and repeated during the time interval 17-21 months.

Cardiopulmonary exercise test for two following days: assessment at baseline and repeated during the time interval 17-21 months.

Gastrointestinal function: assessment at baseline and repeated during the time interval 17-21 months.

  Eligibility

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

Inclusion Criteria:

  • Patients with Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME) according to Canadian diagnostic criteria (Carruthers, 2003)
  • Duration of CFS/ME disease 2-15 years. For patients with mild CFS/ME duration of disease must be 5-15 years.
  • Mild, Mild/Moderate, Moderate, Moderate/Severe and Severe CFS/ME may be included
  • Signed informed consent

Exclusion Criteria:

  • Patients with fatigue, who do not comply with Canadian diagnostic criteria (2003)
  • Duration of CFS/ME < 2 years or >15 years
  • Patients with very severe CFS/ME
  • Pregnancy or lactation.
  • Previous malignant disease (except basal cell carcinoma in skin or uterine cervical dysplasia)
  • Previous treatment with B-lymphocyte depleting therapeutic monoclonal antibodies, such as rituximab
  • Previous long-term systemic immunosuppressive treatment, including drugs such as cyclosporine, azathioprine, mycophenolate mofetil, but except steroid treatment e.g. for obstructive lung disease or for other autoimmune diseases such as ulcerative colitis
  • Severe endogenous depression
  • Lack of ability to adhere to protocol
  • Known multi-allergy with clinically assessed risk from rituximab infusion
  • Reduced kidney function (serum creatinine > 1,5x upper normal level)
  • Reduced liver function (serum bilirubin or transaminases > 1,5x upper normal level)
  • Known HIV positivity, previous hepatitis B or hepatitis C
  • Evidence of ongoing, active and clinically relevant infection
  • Known immunodeficiency with risk from therapeutic B-cell depletion, such as hypogammaglobulinemia
  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: NCT02229942

Locations
Norway
Dept. of Oncology, Haukeland University Hospital
Bergen, Norway, N-5021
Notodden Hospital
Notodden, Norway, N-3675
CFS/ME centre, Oslo University Hospital
Oslo, Norway, N-0424
Division of Rehabilitation Services, University Hospital of North Norway
Tromsø, Norway, N-9038
Dept. of Pain and Complex Disorders, St. Olavs Hospital
Trondheim, Norway, N-7006
Sponsors and Collaborators
Haukeland University Hospital
The Research Council of Norway
Norwegian Department of Health and Social Affairs
The Kavli Foundation
Oslo University Hospital
St. Olavs Hospital
University Hospital of North Norway
Sykehuset Telemark
MEandYou Foundation
The Norwegian ME association
Investigators
Principal Investigator: Olav Mella, MD, PhD Dept. of Oncology, Haukeland University Hospital, Bergen, Norway
  More Information

Publications:
Responsible Party: Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT02229942     History of Changes
Other Study ID Numbers: KTS-6-2014  2014-000795-25  229035 
Study First Received: August 29, 2014
Last Updated: April 11, 2016
Health Authority: Norway: Directorate of Health

Keywords provided by Haukeland University Hospital:
Chronic Fatigue Syndrome (CFS)
Myalgic Encephalitis (ME)
Rituximab
B-lymphocyte depletion
B-cell depletion

Additional relevant MeSH terms:
Syndrome
Fatigue
Encephalitis
Brain Diseases
Fatigue Syndrome, Chronic
Myalgia
Disease
Pathologic Processes
Signs and Symptoms
Central Nervous System Diseases
Nervous System Diseases
Virus Diseases
Muscular Diseases
Musculoskeletal Diseases
Encephalomyelitis
Neuromuscular Diseases
Musculoskeletal Pain
Pain
Neurologic Manifestations
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 06, 2016