Randomized Placebo Controlled Trial of IVIg in Glycine Receptor Antibody Positive Stiff-person Syndrome

Study Overview
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Brief Summary
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This is a randomized double-blind controlled trial of intravenous immunoglobulin (IVIg) for glycine receptor antibody positive (GlyRα1) antibody Stiff Person Syndrome (SPS) spectrum disorders. Adult patients will be enrolled over the course of 36 months. Study duration per patient will be 11 weeks. Total study duration will be 39 months. All treatment and study visits will occur at Mayo Clinic in Rochester, MN.

Detailed Description
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The purpose of this study is to determine whether intravenous immunoglobulin (IVIG) treatment reduces stiffness and spasms in patients with SPS spectrum disorders compared to patients who do not receive any treatment. In this study, investigators want to compare the effects, good and/or bad, of IVIG with placebo on participants with SPS to find out which is better. This is a randomized, double-blind study. Which treatment participants will receive is randomly determined. Participants have an equal chance of receiving IVIG or the placebo. SPS spectrum cohort will include any from the SPS spectrum patient (stiff-limbs, stiff-trunk, stiff-limbs and trunk, and PERM). Study visits will be considered part of clinical care and will occur at: enrollment (will coincide with screening visit), and 11 weeks. IVIg/placebo (saline) treatments will be administered on 2 consecutive days in week 1, week 5, week 9 in all patients.

Official Title
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IVIg in Glycine Receptor Antibody Positive Stiff-person Syndrome (SPS) Spectrum Disorders.

Conditions
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Stiff-Person Syndrome

Intervention / Treatment
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* Drug: Intravenous Immunoglobulins, Human
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patient must be 18 years of age or older Must have symptoms of SPS for less than 3 years If taking corticosteroids, the patients must be on a stabile dose for 30 days prior to enrolment Patients will have a diagnosis of SPS spectrum disorder based on both of clinical and serological status Exclusion Criteria Patients on immune suppressants initiated/dose increased in the prior 6 months History of thrombotic episodes within the 2 years prior to enrollment Known allergic or other severe reactions to blood products including intolerability to previous IVIG Previous adequate trial of IVIG as determined by the Principal Investigator IgA deficiency Reproductive status: Women who are pregnant, breastfeeding Women and men of childbearing potential who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period, as evaluated by the investigator. Any surgical procedure within 4 weeks prior to baseline. Evidence of serious uncontrolled concomitant diseases that may preclude patient participation; Other nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine disease, renal/urologic disease, digestive system disease, congenital or acquired severe immunodeficiency Known active infection within 4 weeks prior to baseline. Evidence of chronic active hepatitis B or C. Active ischemic heart disease in the past year prior to baseline. Patients should not have severe renal or hepatic disease Severe hypertension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous immunoglobulin<br>IVIg dose will be 2g/kg ideal body weight every 4 weeks (in 2 divided doses on consecutive days) for 12 weeks (3 cycles total). | Drug: Intravenous Immunoglobulins, Human<br>* Immunoglobulins are fractionated blood products made from pooled human plasma.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebos<br>* Normal Saline<br>* Other names: Normal Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Distribution-of-stiffness index | Scores on this index range from 0 to 6 and reflect the extent of stiffness. with One point being given for stiffness in each of the following areas: lower trunk, upper trunk, legs, arms, face, and abdomen. Lower scores indicate less stiffness. | Screen, Week 11 | 
| Change in Heightened-sensitivity scale | Scores range from 1 to 7 based on response; one point being given for each source of or type of spasm, as follows: unexpected noises, visual stimuli, somatosensory stimuli, voluntary activities, emotional upset or stress, no specific stimuli, and nocturnal spasms. Lower scores indicate less frequent spasms. | Screen, Week 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GlyRα1, IVIG, stiff-person syndrome, SPS, glycine receptor antibody, intravenous immunoglobulin