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

Sponsor

Mayo Clinic (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03749096

Collaborator

Grifols Biologicals, LLC (Industry)

Enrollment

Location

Arms

4.6

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Stiff-Person Syndrome	Drug: Intravenous Immunoglobulins, Human Drug: Placebos	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Randomized double-blind

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 7, 2018

Actual Primary Completion Date :

Apr 26, 2019

Actual Study Completion Date :

Apr 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
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.
Placebo Comparator: Placebo	Drug: Placebos Normal Saline Other Names: Normal Saline

Arm

Intervention/Treatment

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.

Placebo Comparator: Placebo

Drug: Placebos

Normal Saline

Other Names:

Normal Saline

Outcome Measures

Primary Outcome Measures

Change in Distribution-of-stiffness index [Screen, Week 11]
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.
Change in Heightened-sensitivity scale [Screen, Week 11]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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