Clinical trial NCT02372149: IVIg for Demyelination in Diabetes Mellitus
Official title: Treatment With Gamunex 10% Intravenous Immunoglobulin (IVIg) for Patients With Demyelination and Diabetes Mellitus: A Blinded, Placebo-Controlled Crossover Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Peripheral Neuropathy
Diabetes Mellitus
Chronic Inflammatory Demyelinating Polyneuropathy
Lead sponsor: University of Toronto
Sponsor class: OTHER
Collaborators: name: University Health Network, Toronto
First posted: 2015-02-26
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Overall Neuropathy Limitations Score (ONLS) after 3 months
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Change in Rasch-Built Overall Disability Scale (R-ODS) after 3 months
timeFrame: Baseline and 3 months
measure: Change in Nerve Conduction Studies (NCS) after 3 months
timeFrame: Baseline and 3 months
measure: Change in Medical Research Council (MRC) Sum Score after 3 months
timeFrame: Baseline and 3 months
measure: Change in Grip Strength after 3 months
timeFrame: Baseline and 3 months
measure: Change in Short Form 36 (SF-36) Quality of Life after 3 months
timeFrame: Baseline and 3 months
measure: Adverse Events
timeFrame: 30 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital / Toronto Western Hospital
state: Ontario
Study officials:
affiliation: University of Toronto
name: Ari Breiner, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References: