Intravenous Immunoglobulin and Plasma Exchange in Myasthenia Gravis

NCT01179893 | Completed Phase 4

• 1 other identifier: 07-0280-B
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

Immunomodulation is effective in treating patients with myasthenia gravis (MG), but prior studies have not adequately defined if plasma exchange (PLEX) in superior to intravenous immunoglobulin (IVIG) in the treatment of myasthenia gravis. This study aimed to determine if PLEX was superior to IVIG in the treatment of patients with myasthenia gravis. Patients with MG requiring immunomodulation are randomized to IVIG or PLEX and treated with a full course of immunomodulation. The quantitative myasthenia gravis score (QMGS) will be evaluated as the primary efficacy parameter at day 14 to determine if PLEX is superior to IVIG.

Conditions

Myasthenia Gravid

Keywords

Myasthenia Gravis; IVIG; PLEX

Outcome Measures

Primary Outcomes (1)

• Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 14 after treatment

  QMGS is a validated clinical measure of myasthenia gravis ranging from 0 points (no myasthenic weakness) to a maximum of 39 points, with a defined change of 3.4 units required for clinical significance.

  QMGS at day 14, and patients followed to day 60

Secondary Outcomes (9)

• QMGS Score change at days 21 and 28 from start of treatment.

  28 days

• Post intervention status

  Day 14, 21 and 28

• Single fiber electromyography: jitter, percent abnormal pair, percent blocking

  Days 14 and 28 compared to baseline

• Repetitive Nerve stimulation studies

  Days 14 and 28

• Acetylcholine Receptor Antibody titers

  Day 28 (if positive at baseline)

Study Arms (2)

IVIG

ACTIVE COMPARATOR

Intravenous Immunoglobulin, 2G/Kg, infused over 2 days in the Medical Day Unit of the University Health Network

Biological: IVIG

PLEX

EXPERIMENTAL

Patients received one plasma volume plasma exchanges with 5% albumin replacement fluid. Five plasma exchange procedures occurred every second day with breaks over the weekend allowed. Patients treated in the apheresis units at the University Health Network.

Procedure: PLEX

Interventions

IVIG BIOLOGICAL

Intravenous immunoglobulin

IVIG

PLEX PROCEDURE

Plasma exchange: removal of pathogenic antibodies and constituents and replacement with albumin.

PLEX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years old
• diagnosis of moderate-severe MG (defined as a Quantitative Myasthenia Gravis Score QMGS \>10.5)
• worsening weakness requiring a change in therapy judged by a neuromuscular expert

You may not qualify if:

• Worsening weakness secondary to concurrent medications (e.g. Aminoglycosides)
• Worsening weakness secondary to infection
• Change in corticosteroid dosage in the 2 weeks prior to screening
• Other disorders causing weakness or fatigue
• Known absolute IgA deficiency (risk of anaphylactic reaction to IVIG)
• History of anaphylaxis or severe systemic response to IVIG or albumin
• Pregnancy or breastfeeding
• Active renal failure precluding volume of IVIG (risk of volume overload with IVIG) as judged by the investigators
• Clinically significant cardiac disease precluding IVIG volume as judged by the investigators
• Known hyperviscosity or hypercoaguable state (risk of stroke with IVIG)
• Known coagulopathy with bleeding
• On another current study medication or protocol within 4 weeks of screening
• Patients with known refractory status to either IVIG or PLEX
• Poorly controlled or severe hypertension (exacerbation by IVIG)
• Patient refuses treatment with either IVIG or PLEX

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Grifols Therapeutics LLC: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. Neurology. 2007 Mar 13;68(11):837-41. doi: 10.1212/01.wnl.0000256698.69121.45.

  PMID: 17353471 BACKGROUND

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Immunoglobulins, Intravenous

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Vera Bril, BSc, MD, FRCPC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• David Barth, MD

  University Heatlh Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 9, 2010
• First Posted: August 11, 2010
• Study Start: March 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: August 11, 2010

Record last verified: 2010-08

Locations

CA (1)