Skin-biopsy proven small fiber neuropathy without an underlying cause
Conditions
Interventions
Trade Name: Gamunux 10%
Product Name: Gamunex
Product Code: 726788
Pharmaceutical Form: Infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intra
Sponsors
Maastricht UMC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 18 years or older. • Skin-biopsy proven idiopathic SFN or idiopathic painful neuropathy with predominantly SFN pattern • Pain intensity rated = 5 on the PI-NRS (maximum pain) or on the neuropathic pain scale,36,37 question number 1 for at least 12 weeks before the study as declared by each patient to the best of their knowledge; if available, medical records of each patient will be consulted on the reported pain intensity. • Each subject will receive an information leaflet and an informed consent form. Subjects must give informed consent by signing and dating prior to study entry. • Eligible patients must be willing to complete all study-related activities and examination required by the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Are unable or unwilling to provide written informed consent. • Have predominant clinical picture of large nerve fiber involvement (i.e., weakness, loss of vibration sense, hypo-/areflexia). • Had treatment with IVIg or any other immunomodulatory/immunosuppressive agents (e.g., steroids) within the last 12 weeks prior to the date of informed consent. • Have an underlying cause of SFN (diabetes, SCN9A/10A/11A mutations, hypothyroidism, renal failure, vitamin B12 deficiency, monoclonal gammopathy, alcohol abuse (more than 5 IU/day), malignancies, drugs that cause neuropathy (e.g. chemotherapy, amiodarone, propafenone)). • Have a history of anaphylaxis or severe systemic response to immunoglobulin or with a blood product. • Have cardiac insufficiency (NYHA III/IV), cardiomyopathy, significant cardiac dysrhythmia requiring treatment, unstable or advanced ischemic heart disease, or history of congestive heart failure, severe hypertension (diastolic blood pressure >120 mmHg or systolic >170 mmHg). • Are females who are pregnant, breast-feeding, or if of childbearing potential, or unwilling to practice adequate contraception throughout the study. • Have known hyperviscosity. • Have a history of renal insufficiency or high serum creatinine levels (MDRD <30). • Have known selective IgA deficiency. • Have conditions whose symptoms and effects could alter protein catabolism and/or IgG utilization (e.g. protein-losing enteropathies, nephrotic syndrome). • Have a known hypercoagulable state. • Are mentally challenged adult subjects unable to give independent informed consent. • The use of pain (analgesic/anti-neuropathic) medication is allowed, but only if dosages are remained unchanged for at least 30 days prior to randomization. A change in dosage of these drugs will not be allowed throughout the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of IVIg treatment (4 courses of treatment, 3 weeks apart) compared to placebo by assessing changes on the mean weekly level of peak pain intensity (PI-NRS) compared to baseline scores.;Secondary Objective: Corneal confocal microscopy, pain intensity, pain qualities, and other SFN related complaints, daily and social functioning, as well as quality of life will be assessed. Safety: adverse events, vital signs and laboratory values outside the normal range;Primary end point(s): Comparison of the percentage of responder subjects between the two treatment groups from the first randomization during 12 weeks. A patient withdrawing from the study will be recorded as treatment failure for their randomization arm.;Timepoint(s) of evaluation of this end point: During the complete length of the study (12 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The daily pain intensity (defined as the mean pain experienced during the day: from waking up to 6 pm), the nocturnal pain intensity (6 pm until waking up), and the average of these two will also be assessed using the PI-NRS, twice a week.51 • Change of painful symptoms will be compared to baseline using the patients’ global impression of change (PGIC) on a 7-point Likert scale. Subsequent scores of the PGIC are 1) “worse than ever”; 2) “much worse”; 3) “little worse”; 4) “no change”; 5)”little improved”; 6) “much improved”; 7)”completely resolved”. “Completely resolved” and “much improved” are considered as a relevant improvement. Clinically relevant pain reduction on PGIC for pain will be defined as score 6 (“much improved”) or 7 (“completely resolved”).52,53 • The Rasch-transformed 13 items SFN symptoms inventory questionnaire (RT-SFN-SIQ) highlights sensory symptoms, pain and autonomic complaints.16 Differences between the two arms will be examined using its score obtained after interval transformation using the Rasch method.54,55 • The amount of pain medication used during the trial will be registered in the pain diary and will be used to compare the impact of the treatment versus placebo arms. • Patients will be requested to register (in a pain diary) the frequency and duration of occurrence and duration (in hours)) of non-medical rescue activities as well, such as using cooling/heating and forced resting. • Pain relief will also be captured on a daily basis using a 5-point Likert-scale: 0: no relief, 1: slight, 2: moderate, 3: good, and 4: complete relief. This is according to the IMMPACT recommendations.53 • The neuropathic pain scale (NPS) will also be recorded to determine the various pain qualities.37 • Daily Sleep Interference Scale (DSIS) will also be completed by subject twice a week on waking (11-point numerical scale ranging from 0 (pain does not interfere with sleep) to 10 (pain completely interferes with sleep)). • Rasc | — |
Countries
Netherlands
Contacts
Public ContactC.G. Faber
Maastricht UMC
Outcome results
None listed