Effect of Intravenous Immunoglobulins on Painful Sensory Neuropathy Evaluated by Aggregated N-of-one Trials
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 主要终点
- Pain intensity the second week
研究概览
简要总结
The goal of this clinical trial is to assess effect of Intravenous immunoglobulins (antibodies) as compared to Placebo, on pain intensity in patients from 18-65 years with painful sensory neuropathy without a known cause. Effect of the treatment will be recorded by the patient in a digital diary.
详细描述
Patients suffering from idiopathic sensory neuropathies often report excruciating pain that interferes with daily function and leads to impaired quality of life. Current neuropathic pain treatment options are in general insufficient. Autoimmunity may play a role in some patients, and treatment with intravenous immunoglobulins (IVIG) may have a potential beneficial effect. Available scientific documentation on this topic is limited and disparate.
The main purpose of this trial is to assess effect of IVIG as compared to placebo on pain intensity in patients >18 years with idiopathic painful small fiber neuropathy or sensory neuronopathy.
Each patient will during the 30-week trial period get 3 IVIG courses and 3 placebo courses in a randomized order, given every 5 week on an outpatient basis for three consecutive days. Outcome measures will be recorded by the patient in a digital diary
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Painful sensory neuropathy fulfilling diagnostic criteria for idiopathic small fiber neuropathy or sensory neuronopathy
- •Idiopathic small fiber neuropathy (all of the following)
- •Neuropathic pain (length-dependent/non-length dependent/focal) and at least two of the following clinical signs
- •Hypoesthesia (tactile, pinprick, or thermal)
- •Allodynia (tactile, dynamic, thermal, pressure)
- •Hyperalgesia
- •Aftersensation
- •Normal nerve conduction studies:
- •Reduced intra-epidermal nerve fiber density at the distal leg (IENFD) at the distal leg or Reduced thermal threshold assessed at the foot by QST
- •Causal investigation according to clinical guidelines has not revealed a cause of the neuropathy
- •Sensory neuronopathy (all of the following)
- •Clinical pure sensory neuropathy
- •A score >6.5 on the following
- •Ataxia in the lower or upper limb: 3.1p
- •Asymmetrical distribution of sensory loss: 1.7p IVIGSeN Protocol number 1.2
- •Sensory loss not restricted to the lower limb at full development: 2.0 p
- •At least 1 sensory action potential absent or 3 sensory action potentials <30% of the lower limit of normal in the upper limbs not explained by entrapment neuropathy: 2.8p
- •Less than two nerves with abnormal motor nerve conduction studies in the lower limbs: 3.1p
- •Causal investigation according to clinical guidelines has not revealed a cause of the neuropathy
- •Pain intensity > 5.0 on a pain score from 0-10, lasting at least 4 weeks
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Medical Conditions
- •Previous allergic reaction to IVIG or other blood products)
- •Selective IgA deficiency
- •Cardiac insufficiency (NYHA III/IV ie marked or severe limitation in activity due to symptoms, even during less-than-ordinary activity)
- •Cardiac dysrhythmia requiring treatment
- •Unstable or advanced ischemic heart disease
- •Severe hypertension (diastolic >120 or systolic > 170)
- •Known hyperviscosity
- •Renal insufficiency (GFR < 30 ml/min/1,73m2) or nephrotic syndrome
- •Previous thromboembolic event
- •Prolonged immobilization
- •Hypercoagulable state
- •Prior/Concomitant Therapy
- •Change of pain medication in the 30 days prior to inclusion (unchanged pain medication is allowed, provided dosages stay equal during the study)
- •Treatment with IVIG the last 4 weeks or other ongoing immunomodulatory treatments
- •Use of loop diuretics, Dinutuksimab beta, or Imlifidase Diagnostic assessments
- •Predominant clinical or neurographic features of motor nerve fiber involvement Other Exclusions
- •Females who are breastfeeding, pregnant or unwilling to practice contraception throughout the study
- •Unable to give independent informed consent
研究组 & 干预措施
Intravenous Immunoglobulin
3 courses Intravenous immunoglobulin, Infusion solution, 100mg/ml, 2g/kg over 3 days
干预措施: Intravenous immunoglobulin (Drug)
Placebo
3 courses Saline infusion solution 0,9%, same volume as IVIG over 3 days
干预措施: Placebo (Drug)
结局指标
主要结局
Pain intensity the second week
时间窗: The second week after start of IVIG/Placebo infusions (mean of days 8, 10 and 13)
Pain intensity after IVIG/Placebo infusions scored on a numeric rating scale (NRS) ranging from 0 to 10
次要结局
- Pain intensity across 4 weeks(Day 8 to 34 after start of each infusion)
- Anti-FGF3 antibodies(Before start of infusion of IVIG/Placebo week 1, 5, 11, 16, 21 and 26)
- Disability and quality of life(At the end of the third week after infusion)
- Adverse events(From start to end of interventions week 1 - 30)