Treatment With Gamunex 10% Intravenous Immunoglobulin (IVIg) for Patients With Demyelination and Diabetes Mellitus: A Blinded, Placebo-Controlled Crossover Pilot Study
试验速览
- 阶段
- 4 期
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in Overall Neuropathy Limitations Score (ONLS) after 3 months
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •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.
研究组 & 干预措施
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
干预措施: 10% intravenous immunoglobulin (IVIg) (Drug)
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
干预措施: 0.9% sodium chloride (Drug)
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)
干预措施: 10% intravenous immunoglobulin (IVIg) (Drug)
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)
干预措施: 0.9% sodium chloride (Drug)
结局指标
主要结局
Change in Overall Neuropathy Limitations Score (ONLS) after 3 months
时间窗: Baseline and 3 months
ONLS score will be measured before and after 3 months of IVIg / placebo
次要结局
- Change in Nerve Conduction Studies (NCS) after 3 months(Baseline and 3 months)
- Change in Rasch-Built Overall Disability Scale (R-ODS) after 3 months(Baseline and 3 months)
- Change in Medical Research Council (MRC) Sum Score after 3 months(Baseline and 3 months)
- Change in Short Form 36 (SF-36) Quality of Life after 3 months(Baseline and 3 months)
- Adverse Events(30 days)
- Change in Grip Strength after 3 months(Baseline and 3 months)
研究者
Ari Breiner, MD
Assistant Professor of Medicine (Neurology)
University of Toronto