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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Stiff-Person Syndrome
• Intervention / Treatment: Drug: Intravenous Immunoglobulins, Human; Drug: Placebos

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebos; Normal Saline; Other Names: Normal Saline
Active Comparator: Intravenous immunoglobulin; 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; Immunoglobulins are fractionated blood products made from pooled human plasma.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Grifols Biologicals, LLC
• Investigators: Principal Investigator: Andrew McKeon, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2018
• Primary Completion (Actual): April 26, 2019
• Study Completion (Actual): April 26, 2019

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (Actual): November 21, 2018

Study Record Updates

• Last Update Posted (Actual): June 13, 2019
• Last Update Submitted That Met QC Criteria: June 11, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: IVIG; intravenous immunoglobulin; SPS; stiff-person syndrome; glycine receptor antibody; GlyRα1
• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Disease; Neuromuscular Diseases; Spinal Cord Diseases; Syndrome; Stiff-Person Syndrome; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 18-007041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No