IVIG in Painful Sensory Neuropathy

Phase 4

Not yet recruiting

• Conditions: Small Fiber Neuropathy; Sensory Neuropathy
• Interventions: Drug: Placebo; Drug: Intravenous immunoglobulin

• Registration Number: NCT06183008
• Lead Sponsor: Sorlandet Hospital HF

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

Study Timeline

• Status Verified: 2023-03
• Study First Submitted: 2023-12-13
• Study First Submitted QC: 2023-12-13
• Last Update Submitted: 2023-12-13
• Study First Posted: 2023-12-27
• Last Update Posted: 2023-12-27
• Study Start: 2024-02
• Primary Completion: 2028-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	3 courses Saline infusion solution 0,9%, same volume as IVIG over 3 days
Intravenous Immunoglobulin	Intravenous immunoglobulin	3 courses Intravenous immunoglobulin, Infusion solution, 100mg/ml, 2g/kg over 3 days

Primary Outcome Measures

Name	Time	Method
Pain intensity the second week	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

Secondary Outcome Measures

Name	Time	Method
Pain intensity across 4 weeks	Day 8 to 34 after start of each infusion	Pain intensity across 4 weeks after start of each infusion (mean of scoring three times per week from)
Anti-FGF3 antibodies	Before start of infusion of IVIG/Placebo week 1, 5, 11, 16, 21 and 26	Blood samples will be tested for anti-FGF3 antibodies to evaluate their association with the observed clinical response in terms of pain relief to IVIG.
Disability and quality of life	At the end of the third week after infusion	Scored on: Polyneuropathy Patient-reported Index (CAPPRI)
Adverse events	From start to end of interventions week 1 - 30	Recording adverse events