IVIg for Demyelination in Diabetes Mellitus

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Inflammatory Demyelinating Polyneuropathy, Peripheral Neuropathy, Diabetes Mellitus

Intervention / Treatment
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* Drug: 10% intravenous immunoglobulin (IVIg)
* Drug: 0.9% sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Diabetes, as per American Diabetes Association Criteria. Clinical evidence of polyneuropathy and NCS shows 2 separate motor nerves (median, ulnar, tibial, or peroneal) which meet criteria for demyelination, defined as follows: Conduction velocity <90% lower limit of normal (LLN), distal latency >110% upper limit of normal (ULN), or minimal F-wave latency >110% ULN The changes are not exclusively due to median neuropathy at the wrist, ulnar neuropathy at the elbow, or peroneal neuropathy at the fibular head. Clinical suspicion of possible demyelinating polyneuropathy (CIDP). Exclusion Criteria: Pregnant patients, or those of childbearing potential not using contraception. Patients <18 years of age. 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. 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. 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. Presence of concomitant neurological illness, which may confound evaluation. Fails or unable to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IVIg--Washout--0.9% NaCl (CROSSOVER)<br>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: 10% intravenous immunoglobulin (IVIg)<br> <br> * Other names: Gamunex;Drug: 0.9% sodium chloride<br> <br> * Other names: Normal Saline;|
| Experimental: 0.9% NaCl--Washout--IVIg (CROSSOVER)<br>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: 10% intravenous immunoglobulin (IVIg)<br> <br> * Other names: Gamunex;Drug: 0.9% sodium chloride<br> <br> * Other names: Normal Saline;|

What is the study measuring?
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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 |