Treatment of Multiple System Atrophy Using Intravenous Immunoglobulins

Multiple System Atrophy (MSA) is a progressive sporadic neurodegenerative disorder leading to widespread loss of brain cells that results in parkinsonian, cerebellar and autonomic dysfunction. The cause of the MSA remains unclear. Available treatment is symptomatic only and does not alter the course of disease.

Although the cause of MSA remains unclear, there is evidence of presence of common neuroinflammatory mechanisms in the MSA brains including activation of microglia and production of toxic cytokines. This research protocol is based on hypothesis that the MSA progression can be altered by blocking the neuroinflammatory activity.

This protocol includes administration of intravenous immunoglobulin (IVIg). IVIg contains antibodies derived from human plasma which can block the inflammatory responses in the brain that can lead to loss of brain cells.

Study Overview

• Status: Completed
• Conditions: Multiple System Atrophy
• Intervention / Treatment: Drug: intravenous immunoglobulin (IVIg)

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female older than 17 years.
2. Clinical diagnosis of probable multiple system atrophy
3. Provide written informed consent to participate in the study
4. Understand that they may withdraw their consent at any time

Exclusion Criteria:

1. Women who are pregnant or lactating
2. In the investigator's opinion, have any other significant systemic, hepatic, cardiac or renal illness.
3. In the investigator's opinion, the subjects are significantly dehydrated, as determined by clinical evaluation including measurement of skin turgor, blood urea nitrogen and creatinine values.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Interventions included monthly infusions of intravenous immunoglobulin.	Drug: intravenous immunoglobulin (IVIg); The intravenous immunoglobulin (brand Privigen) will be infused intravenously, monthly, 6 times, for 6 months the dose will be 0.4 gram/kg for each infusion.; Other Names: Privigen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events up to Six Months Post-treatment	The primary outcome measure was to evaluate the safety and tolerability of the IVIG infusions in patients with multiple system atrophy. The primary endpoint was defined as the frequency of adverse events (AE). AEs including their severity and relationship to the IVIG were assessed throughout the study and at least 60 days after the last infusion. The AEs were considered to be related to the IVIG infusion (infusional AE) if they occurred during an infusion or within 72 hours afterwards. Non-infusional AEs were further classified as possible related to IVIG or likely not related to IVIG. Serious AEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization. Any AE was defined as occurrence of any symptom regardless of intensity grade.	Monthly, up to 8 months (including the screening visit and the final visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary Efficacy of IVIg for Treatment of MSA.	The secondary outcome measure was to evaluate the preliminary efficacy of IVIG for the treatment of MSA. The primary efficacy endpoint was change of the Unified MSA Rating Scale (UMSARS-I and UMSAR-II) compared to baseline. UMSARS-I and UMSARS-II are validated semiquantitative rating scales for evaluation of severity of MSA. UMSARS-I comprises a historical review of disease-related impairments and UMSARS-II comprises motor examination. UMSARS-I has 12 questions, each with assigned score 0-4, where 0 is normal and > are abnormal responses. Total range of UMSARS-I is 0 to 48. UMSARS-II has 12 items rated by an examiner, each with assigned score 0-4, where 0 is normal and > are abnormal responses. Total range of UMSARS-II is 0 to 56. The scores of UMSARS-I and UMSARS-II at baseline (month 1) was compared with the scores obtained at the final visit (month 8) which was 8 months apart. The interventions occured at months 2-7, total six times.	Monthly, up to 8 months (including the screening visit and the final visit)

Collaborators and Investigators

• Sponsor: University of Massachusetts, Worcester
• Investigators: Principal Investigator: Peter Novak, MD, PhD, University of Massachusetts, Worcester

Publications and helpful links

General Publications

• Novak P, Williams A, Ravin P, Zurkiya O, Abduljalil A, Novak V. Treatment of multiple system atrophy using intravenous immunoglobulin. BMC Neurol. 2012 Nov 1;12:131. doi: 10.1186/1471-2377-12-131.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: September 9, 2008
• First Submitted That Met QC Criteria: September 9, 2008
• First Posted (Estimate): September 11, 2008

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 5, 2017
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: multiple system atrophy, MSA,; intravenous immunoglobulin, IVIg
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Atrophy; Multiple System Atrophy; Shy-Drager Syndrome; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: H-12784