Rituximab in Chronic Inflammatory Demyelinating Polyneuropathy
- Conditions
- Chronic Inflammatory Demyelinating Polyneuropathy
- Interventions
- Registration Number
- NCT04480450
- Lead Sponsor
- University of Kansas Medical Center
- Brief Summary
CIDP is a heterogeneous disease with variable responses to therapy. Recently, a distinctive subgroup of patients with serum autoantibodies to the paranodal proteins contactin and neurofascin have been identified. Although they present with active and serious disease, multiple clinical reports suggest that these patients can be cured with a treatment that depletes B cells and presumably eliminates pathogenic autoantibodies. However, beyond that subgroup of CIDP patients, which CIDP patients might benefit from Rituximab and B cell depletion is unknown. This Phase II study will treat 3 homogenous groups of 16 CIDP patients each with Rituximab in order to determine if there are subgroups that can be taken off current medications and put into long-term remission. The results from this study will be used to design a future larger trial. Biomarkers including paranodal antibodies, serum neurofilament light chains, anti-ganglioside antibodies will be obtained in order to learn about disease pathogenesis and possibly target therapy
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 44
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IVIg/SCIg < 3 Years Arm Rituximab Patients with CIDP successfully treated with IVIg/SCIg for under 12 months. Subjects will receive an intravenous infusion of 1,000mg Rituximab at Week 0 and Week 2. IVIg/SCIg > 3 Years Arm Rituximab Patients with CIDP successfully treated with IVIg/SCIg for more than 12 months. Subjects will receive an intravenous infusion of 1,000mg Rituximab at Week 0 and Week 2.
- Primary Outcome Measures
Name Time Method Inflammatory Neuropathy Cause and Treatment (INCAT) Disability Score 48 Weeks The INCAT disability scale captures upper and lower limb dysfunction separately on a scale of 0 to 5, which are then added together for a total composite score ranging between 0 and 10.15 Lower scores indicate no or minimal disability (no arm dysfunction or walking abnormality), and higher scores indicate more disability (no purposeful arm movement or restricted to wheelchair). The adjusted INCAT disability score is identical to the INCAT disability score with the exception that changes in upper limb function from 0 (normal) to 1 (minor symptoms) are excluded. This exclusion was made because upper limb changes from 0 to 1 (minor symptoms in the fingers which do not impair any functional activities) were not judged by regulatory agencies to be clinically significant in all patients. With the exception of a change in the upper limb score from 0 to 1, all other 1 point changes in the INCAT score are considered clinically significant.
- Secondary Outcome Measures
Name Time Method Inflammatory-Rasch-built Overall Disability Scale (I-RODS) 48 Weeks The Rasch built overall disability scale for immune-mediated peripheral neuropathies (I-RODS) is a patient-based, linearly weighted scale that captures activity and social participation limitations in patients with CIDP.16 The assessment includes 24 questions that address upper and lower limb disability. These range in difficulty from ability to read a book, eat, or brush teeth to dance, stand for hours, and run. Participants are asked to indicate if they can easily perform the task, perform it with difficulty, or are unable to perform it at all. Both the ability of the patient and the perceived difficulty of a task are tallied for a raw R-ODS score that ranges between 0 (complete disability) and 48 (no disability). The resulting raw I-RODS score are then be transformed to a final I-RODS score ranging from 0 (severe disability) to 100 (no disability). A change in the I-RODS scores of ≥ 4 points (using the centile metric) is considered clinically meaningful.
Visual Analog Pain Severity Scale (VAS) 48 Weeks The pain VAS is a validated sensitive linear scale that has been widely used to assess pain in diverse populations of patients.18 The scale is comprised of a horizontal or vertical line, 10 centimeters in length, anchored by 2 verbal descriptors, one for each symptom extreme. A score of 0 indicates "no pain" while a score of 100 (100 mm scale) indicates "pain as bad as it could be" or "worst imaginable pain". The pain VAS is self-completed by the respondent by placing a line perpendicular to the VAS line at the point that represents their pain intensity. The score is determined by measuring the distance (mm) on the 10-cm line between the "no pain" anchor and the patient's mark, providing a range of scores from 0-100. Higher scores indicate greater pain intensity
Martin vigorimeter grip strength 48 Weeks Grip strength provides a quantitative objective measure of grip strength and an instant measure of strength impairment. The Vigorimeter from Martin is a hand-held device that measures grip strength by recording the pressure generated from squeezing a rubber bulb. The rubber bulb is placed in the hand between the palm and the thumb and index fingers. Pressure expressed in Kilopascal is recorded with a nanometer. A result is obtained after the subject squeezes 3 times with each hand. The mean grip strength of three squeezes is recorded in each hand.
Modified Fatigue Severity Scale (mFSS) 48 Weeks The fatigue severity scale (FSS) is one available tool to measure fatigue.17 FSS is a Rasch-built patient self-assessment questionnaire that measures fatigue severity and impact on activities and lifestyle by asking participants to respond to 7 separate items. Responses are scored on a 4-point scale (0= strongly disagree, 3 = strongly agree) with a total score range from 0 to 21. Higher scores indicate more fatigue.
Medical Research Council (MRC) Sum Score 48 Weeks The MRC sum score is determined by assessing the following 8 muscle pairs: bilateral shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, index finger abduction, great toe dorsiflexion and foot dorsiflexion. The MRC sum score is a summation of the MRC grades (range 0 to 5 with 0 = paralysis; 1 = only a trace or flicker of muscle contraction is seen or felt; 2 = muscle movement is possible with gravity eliminated; 3 = muscle movement is possible against gravity; 4 = muscle strength is reduced, but movement against resistance is possible and 5 = normal strength given in full numbers. The MRC sum score ranges from 0 ("total paralysis") to 60 ("normal strength").
EuroQOL-5D 48 Weeks The EuroQOL-5D is a simple survey meant to assess quality of life in a wide range of health conditions.23 The measure has 2 parts. In the first part 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) are assessed by 1 of 5 levels of impairment: no problems, slight problems, moderate problems, severe problems, or extreme problems. The second part of the survey is a visual analogue scale assessing overall health on the day of assessment. The EuroQOL-5D has been extensively validated in numerous therapeutic areas and has been found to be sensitive, reliable, and have good internal consistency.