IVIg for Demyelination in Diabetes Mellitus (IDIDM)

University of Toronto

Status and phase: Unknown; Phase 4

Conditions: Peripheral Neuropathy; Chronic Inflammatory Demyelinating Polyneuropathy; Diabetes Mellitus

Treatments: Drug: 10% intravenous immunoglobulin (IVIg); Drug: 0.9% sodium chloride

Study type: Interventional

Funder types: Other

Identifiers

NCT02372149

14-8297-B

Details and patient eligibility

About

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.

Full 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.

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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25 participants in 2 patient groups

IVIg--Washout--0.9% NaCl (CROSSOVER)

Experimental group

Description:

1. 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) 2. Washout period 3. 0.9% sodium chloride in water - equal volume to IVIg - Monthly x4

Treatment:

Drug: 0.9% sodium chloride

Drug: 10% intravenous immunoglobulin (IVIg)

0.9% NaCl--Washout--IVIg (CROSSOVER)

Experimental group

Description:

1. 0.9% sodium chloride in water - equal volume to IVIg - Monthly x4 2. Washout period 3. 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)

Treatment:

Drug: 0.9% sodium chloride

Drug: 10% intravenous immunoglobulin (IVIg)