Clinical trial NCT06183008: IVIG in Painful Sensory Neuropathy
Official title: Effect of Intravenous Immunoglobulins on Painful Sensory Neuropathy Evaluated by Aggregated N-of-one Trials
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Sensory Neuropathy
Small Fiber Neuropathy
Keywords: nervous system diseases
neuromuscular diseases
peripheral nervous system diseases
small fiber neuropathy
sensory neuronopathy
sensory neuropathy
IVIG
Intravenous immunoglobulin
n-of-1
Sørlandet sykehus
Sorlandet hospital
Kristiansand
polyneuropathy
Intravenous immune globulin
Lead sponsor: Sorlandet Hospital HF
Sponsor class: OTHER_GOV
Collaborators: name: Oslo University Hospital
name: University Hospital of North Norway
name: University Hospital of Saint-Etienne
First posted: 2023-12-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: N-of-one trial, individual randomized, double-blind, and multiple crossover comparisons of an interventional treatment and placebo
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

Painful sensory neuropathy fulfilling diagnostic criteria for idiopathic small fiber neuropathy or sensory neuronopathy

* Idiopathic small fiber neuropathy (all of the following)

  1. Neuropathic pain (length-dependent/non-length dependent/focal) and at least two of the following clinical signs

     1. Hypoesthesia (tactile, pinprick, or thermal)
     2. Allodynia (tactile, dynamic, thermal, pressure)
     3. Hyperalgesia
     4. Aftersensation
  2. Normal nerve conduction studies:
  3. 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
  4. Causal investigation according to clinical guidelines has not revealed a cause of the neuropathy
* Sensory neuronopathy (all of the following)

  1. Clinical pure sensory neuropathy
  2. A score \>6.5 on the following

     1. Ataxia in the lower or upper limb: 3.1p
     2. Asymmetrical distribution of sensory loss: 1.7p IVIGSeN Protocol number 1.2
     3. Sensory loss not restricted to the lower limb at full development: 2.0 p
     4. 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
     5. Less than two nerves with abnormal motor nerve conduction studies in the lower limbs: 3.1p
  3. 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

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1. Previous allergic reaction to IVIG or other blood products)
2. Selective IgA deficiency
3. Cardiac insufficiency (NYHA III/IV ie marked or severe limitation in activity due to symptoms, even during less-than-ordinary activity)
4. Cardiac dysrhythmia requiring treatment
5. Unstable or advanced ischemic heart disease
6. Severe hypertension (diastolic \>120 or systolic \> 170)
7. Known hyperviscosity
8. Renal insufficiency (GFR \< 30 ml/min/1,73m2) or nephrotic syndrome
9. Previous thromboembolic event
10. Smoking
11. Diabetes
12. Prolonged immobilization
13. Hypercoagulable state

    Prior/Concomitant Therapy
14. Change of pain medication in the 30 days prior to inclusion (unchanged pain medication is allowed, provided dosages stay equal during the study)
15. Treatment with IVIG the last 4 weeks or other ongoing immunomodulatory treatments
16. Use of loop diuretics, Dinutuksimab beta, or Imlifidase Diagnostic assessments
17. Predominant clinical or neurographic features of motor nerve fiber involvement Other Exclusions
18. Females who are breastfeeding, pregnant or unwilling to practice contraception throughout the study
19. Unable to give independent informed consent

Primary outcomes:
measure: Pain intensity the second week
timeFrame: The second week after start of IVIG/Placebo infusions (mean of days 8, 10 and 13)
Secondary outcomes:
measure: Pain intensity across 4 weeks
timeFrame: Day 8 to 34 after start of each infusion
measure: Disability and quality of life
timeFrame: At the end of the third week after infusion
measure: Anti-FGF3 antibodies
timeFrame: Before start of infusion of IVIG/Placebo week 1, 5, 11, 16, 21 and 26
measure: Adverse events
timeFrame: From start to end of interventions week 1 - 30
Other outcomes:
Locations:
Study officials:
affiliation: Sorlandet Hospital HF, Department of Neurology
name: Jon-Marius Ørnes, Cand.med
role: PRINCIPAL_INVESTIGATOR
affiliation: Sorlandet Hospital HF, Department of Neurology
name: Unn Ljøstad, Cand.med PhD
role: STUDY_DIRECTOR
affiliation: Sorlandet Hospital HF, Department of Neurology
name: Åse Mygland, Cand.med PhD
role: STUDY_DIRECTOR
References: