IVIG in Painful Sensory Neuropathy

NCT ID: NCT06183008

Last Updated: 2023-12-27

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-29
• Study Completion Date: 2028-12-31

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

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Intravenous Immunoglobulin

3 courses Intravenous immunoglobulin, Infusion solution, 100mg/ml, 2g/kg over 3 days

Group Type: EXPERIMENTAL

Intravenous immunoglobulin

Intervention Type: DRUG

Each patient will during the 30-week trial period get 3 IVIG courses (each total dose 2g/kg) for three consecutive days

Placebo

3 courses Saline infusion solution 0,9%, same volume as IVIG over 3 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Each patient will during the 30-week trial period get 3 placebo courses (each 0.9% saline similar volume) for three consecutive days

Interventions

Intravenous immunoglobulin

Each patient will during the 30-week trial period get 3 IVIG courses (each total dose 2g/kg) for three consecutive days

Intervention Type: DRUG

Placebo

Each patient will during the 30-week trial period get 3 placebo courses (each 0.9% saline similar volume) for three consecutive days

Intervention Type: DRUG

Other Intervention Names

IVIG; Privigen; 0.9% saline

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oslo University Hospital

OTHER

Sponsor Role: collaborator

University Hospital of North Norway

OTHER

Sponsor Role: collaborator

University Hospital of Saint-Etienne

OTHER

Sponsor Role: collaborator

Sorlandet Hospital HF

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jon-Marius Ørnes, Cand.med

Role: PRINCIPAL_INVESTIGATOR

Sorlandet Hospital HF, Department of Neurology

Unn Ljøstad, Cand.med PhD

Role: STUDY_DIRECTOR

Sorlandet Hospital HF, Department of Neurology

Åse Mygland, Cand.med PhD

Role: STUDY_DIRECTOR

Sorlandet Hospital HF, Department of Neurology

Central Contacts

Ørnes

Role: CONTACT

Phone: +47 38125396

Email: Jon-Marius.Rognhaug.Ornes@sshf.no

Unn Ljøstad

Role: CONTACT

Phone: +47 38073908

Email: Unn.Ljostad@sshf.no

Other Identifiers

IVIGSeN

Identifier Type: -

Identifier Source: org_study_id