IVIG in Painful Sensory Neuropathy

Small Fiber Neuropathy Clinical Trial

Official title:

Effect of Intravenous Immunoglobulins on Painful Sensory Neuropathy Evaluated by Aggregated N-of-one Trials

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06183008
• Other study ID #: IVIGSeN
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: February 2024
• Est. completion date: December 2028

Study information

• Verified date: March 2023
• Source: Sorlandet Hospital HF
• Contact: Ørnes
• Phone: +47 38125396
• Email: Jon-Marius.Rognhaug.Ornes[@]sshf.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Peripheral Nervous System Diseases
• Sensory Neuropathy
• Small Fiber Neuropathy

Intervention

Drug:
• Intravenous immunoglobulin
Each patient will during the 30-week trial period get 3 IVIG courses (each total dose 2g/kg) for three consecutive days
• Placebo
Each patient will during the 30-week trial period get 3 placebo courses (each 0.9% saline similar volume) for three consecutive days

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Sorlandet Hospital HF	Oslo University Hospital, University Hospital of North Norway, University Hospital of Saint-Etienne

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain intensity the second week	Pain intensity after IVIG/Placebo infusions scored on a numeric rating scale (NRS) ranging from 0 to 10	The second week after start of IVIG/Placebo infusions (mean of days 8, 10 and 13)
Secondary	Pain intensity across 4 weeks	Pain intensity across 4 weeks after start of each infusion (mean of scoring three times per week from)	Day 8 to 34 after start of each infusion
Secondary	Disability and quality of life	Scored on: Polyneuropathy Patient-reported Index (CAPPRI)	At the end of the third week after infusion
Secondary	Anti-FGF3 antibodies	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.	Before start of infusion of IVIG/Placebo week 1, 5, 11, 16, 21 and 26
Secondary	Adverse events	Recording adverse events	From start to end of interventions week 1 - 30