IVIg for Demyelination in Diabetes Mellitus (IDIDM)

Treatment With Gamunex 10% Intravenous Immunoglobulin (IVIg) for Patients With Demyelination and Diabetes Mellitus: A Blinded, Placebo-Controlled Crossover Pilot Study

The purpose of this study is to determine whether intravenous immunoglobulin (IVIg) is an effective intervention for patients with diabetes, peripheral neuropathy, and demyelination on nerve conduction studies. All patients will receive both IVIg and placebo for 3 months each, with a 3 month washout period in between.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus; Peripheral Neuropathy; Chronic Inflammatory Demyelinating Polyneuropathy
• Intervention / Treatment: Drug: 0.9% sodium chloride; Drug: 10% intravenous immunoglobulin (IVIg)

Detailed Description

There is a knowledge gap with regards to the appropriate method of detecting and treating chronic inflammatory demyelinating polyneuropathy (CIDP), in patients with co-existent diabetes. In this pilot study the investigators plan to examine the overlap between diabetic polyneuropathy and CIDP by treating patients with diabetes and demyelinating abnormalities using IVIg. The investigators will enroll diabetes patients with a broad spectrum of demyelinating abnormalities.

The proposed trial will be an explanatory, blinded, single-centre, superiority, randomized controlled cross-over trial. Each patient will receive 3 months of 10% intravenous immunoglobulin and 3 months of placebo (0.9% sodium chloride in water) with a 3-month washout period. The primary outcome measure is the mean change in ONLS (Overall Neuropathy Limitation Scale), a measure of disability in polyneuropathy; however secondary outcome measures will consider impairments and quality of life.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eduardo Ng, MD; Phone Number: 416-340-4184; Email: eduardo.ng@uhn.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Recruiting
      • Toronto General Hospital / Toronto Western Hospital
      • Contact: Eduardo Ng, MD; Phone Number: 416-340-4184; Email: eduardo.ng@uhn.ca

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:

1. Age ≥18 years.
2. Diabetes, as per American Diabetes Association Criteria.

3. Clinical evidence of polyneuropathy and NCS shows 2 separate motor nerves (median, ulnar, tibial, or peroneal) which meet criteria for demyelination, defined as follows:

   1. Conduction velocity <90% lower limit of normal (LLN), distal latency >110% upper limit of normal (ULN), or minimal F-wave latency >110% ULN
   2. The changes are not exclusively due to median neuropathy at the wrist, ulnar neuropathy at the elbow, or peroneal neuropathy at the fibular head.
4. Clinical suspicion of possible demyelinating polyneuropathy (CIDP).

Exclusion Criteria:

1. Pregnant patients, or those of childbearing potential not using contraception.
2. Patients <18 years of age.
3. Presence of an alternative etiology of peripheral neuropathy, such as: hereditary neuropathies (Charcot Marie-Tooth disease); B-vitamin deficiency- or excess-related neuropathy; uremic neuropathy; neuropathy secondary to monoclonal gammopathy; history of cancer- or chemotherapy-related neuropathy; other toxin exposures; and alcoholic neuropathy.
4. Contraindication to IVIg, including: history of recurrent thrombosis, immunoglobulin A deficiency, or severe hypersensitivity reaction to IVIg in past, renal failure, recurrent deep venous thrombosis, pulmonary embolus, stroke, or myocardial infarction.
5. Presence of serious or unstable medical condition, which may preclude study completion or lead to inability to tolerate IVIg. This may include active heart failure, uncontrolled hypertension, or severe anemia, among other conditions.
6. Presence of concomitant neurological illness, which may confound evaluation.
7. Fails or unable to provide informed consent.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IVIg--Washout--0.9% NaCl (CROSSOVER); 10% caprylate-chromatography purified intravenous immunoglobulin (IVIg) Initial dose: 1.0gm/kg/day for 2 days (maximum 80gm/day). Maintenance dose (monthly x3): 1.0mg/kg/day for 1 day (maximum 80gm/day); Washout period; 0.9% sodium chloride in water - equal volume to IVIg - Monthly x4	Drug: 0.9% sodium chloride; Other Names: Normal Saline; Drug: 10% intravenous immunoglobulin (IVIg); Other Names: Gamunex
Experimental: 0.9% NaCl--Washout--IVIg (CROSSOVER); 0.9% sodium chloride in water - equal volume to IVIg - Monthly x4; Washout period; 10% caprylate-chromatography purified intravenous immunoglobulin (IVIg) Initial dose: 1.0gm/kg/day for 2 days (maximum 80gm/day). Maintenance dose (monthly x3): 1.0mg/kg/day for 1 day (maximum 80gm/day)	Drug: 0.9% sodium chloride; Other Names: Normal Saline; Drug: 10% intravenous immunoglobulin (IVIg); Other Names: Gamunex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Overall Neuropathy Limitations Score (ONLS) after 3 months	ONLS score will be measured before and after 3 months of IVIg / placebo	Baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Rasch-Built Overall Disability Scale (R-ODS) after 3 months	R-ODS score will be measured before and after 3 months of IVIg / placebo	Baseline and 3 months
Change in Nerve Conduction Studies (NCS) after 3 months	Changes in NCS parameters will be compared before and after 3 months of IVIg / placebo	Baseline and 3 months
Change in Medical Research Council (MRC) Sum Score after 3 months	MRC sum score will be compared before and after 3 months of IVIg / placebo	Baseline and 3 months
Change in Grip Strength after 3 months	Grip strength (using Martin vigorimeter) will be compared before and after 3 months of IVIg / placebo	Baseline and 3 months
Change in Short Form 36 (SF-36) Quality of Life after 3 months	SF-36 will be compared before and after 3 months of IVIg / placebo	Baseline and 3 months
Adverse Events	Number of adverse events and serious adverse events within 30 days of IVIg administration	30 days

Collaborators and Investigators

• Sponsor: University of Toronto
• Collaborators: University Health Network, Toronto
• Investigators: Principal Investigator: Ari Breiner, MD, FRCPC, University of Toronto

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): February 1, 2018
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: February 12, 2015
• First Submitted That Met QC Criteria: February 19, 2015
• First Posted (Estimate): February 26, 2015

Study Record Updates

• Last Update Posted (Estimate): November 11, 2016
• Last Update Submitted That Met QC Criteria: November 10, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Endocrine System Diseases; Neuromuscular Diseases; Polyradiculoneuropathy; Diabetes Mellitus; Peripheral Nervous System Diseases; Polyneuropathies; Demyelinating Diseases; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 14-8297-B