Idiopathic Small Fiber Neuropathy
Conditions
Brief summary
The purpose of this study is to assess safety and efficacy of treatment with pregabalin in patients with idiopathic small fiber neuropathy proven by skin biopsy.This is an enriched enrollment randomized withdrawal study that comprises 4 phases: a screening and selection phase, a washout period from previous pain medication for enriched enrollment, an 8 week single blind pregabalin treatment phase; and a 4 week randomized withdrawal phase.
Detailed description
Patients who show any increase in their pain intensity score during the washout phase will be eligible for the single blind pregabalin treatment phase. Patients who respond to pregabalin, with at least 1 point improvement in neuropathic pain from baseline at the end of the single blind pregabalin treatment phase and meeting all other study requirements are considered eligible for participation in the withdrawal phase. These eligible patients are randomly assigned (1:1) to continue pregabalin or to be switched to placebo for a comparison of pregabalin efficacy and safety. Patients who have a worsening of average pain relative to the last week of the single blind pregabalin treatment period by more than one point and average pain level \> =4 will be considered to have a loss of therapeutic response (LTR).
Interventions
DRUGPregabalin
Pregabalin will be given to the patients, starting at 75 mg BID and increased weekly to reach 225 mg BID for 8 weeks. During withdrawal phase, dose of pregabalin will be kept the same for patients who are randomized to the pregabalin withdrawal group.
DRUGPlacebo
Placebo will be given to the patients that are randomized to placebo during withdrawal phase.
Sponsors
Pfizer
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with idiopathic predominate-small fiber neuropathy * Subject must have chronic peripheral neuropathic pain for more than 3 months * A score \>3 and \<8 on Pain intensity scale for pain in prior week at first visit; * Show increase in pain intensity scores during the wash off period; * Age older than 18 years;
Exclusion criteria
* Subjects with large-fiber predominant neuropathy * Subjects with HIV infection, trigeminal neuralgia (TGN), toxic neuropathy (e.g. chemotherapy exposure), paraneoplastic neuropathy, mono-gammopathy, inflammatory neuropathy, celiac disease, systemic lupus, peripheral vascular disease, connective tissue disorders, hepatitis C, Fabry disease, and diabetes; * Subjects with uncontrolled thyroid or B12 disorders * Subjects with Complex Regional Pain Syndrome * Allergy to Pregabalin * Subjects at risk of suicide or self harm * Subjects with any clinically unstable cardiovascular, hematological, autoimmune, endocrine, renal, hepatic, renal, respiratory, or gastrointestinal disease; epilepsy, symptomatic peripheral vascular disease including intermittent claudication, pernicious anemia, untreated hypothyroidism, venous insufficiency, or spinal stenosis. * History of known analgesic, alcohol or illicit drug abuse within 12 months of first visit; * Pregnant females; breastfeeding females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Score for Pain Intensity. | Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase | The primary outcome is change in visual analogue score for pain, with 0 being no pain at all and 10 being the most severe pain and a higher score meaning more pain, after 8 weeks of treatment phase and 4 weeks of randomized withdrawal phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brief Pain Inventory (BPI sf); | Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase | Brief pain inventory is a scoring system for average pain intensity on scale of 0-10 with higher number meaning more pain. |
| Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase | a scoring system describing sleep quality between 0-10 with 0 having no problem with sleep and 10 not being to sleep at all. |
| Patient Global Impression of Change (PGIC); | At 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase | patient assign a number between 1-7 to the level of improvement, 1 showing substantial improvement and 7 showing no improvement at all. |
Countries
United States
Participant flow
Recruitment details
11 subjects were recruited in the study.
Pre-assignment details
Each subject underwent a washout period to stop the the current pain medications. Subjects who had significant reduction in pain were randomized to either placebo or Lyrica during the double blind withdrawal phase.
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin Treatment/Pregabalin Withdrawal All patients will were with pregabalin. after 8 weeks of treatment, they were randomized to continue on pregabalin. | 3 |
| Pregabalin Treatment/ Placebo Withdrawal After finishing the pregabalin treatment phase for 8 weeks, these patients were randomized to the placebo arm for the withdrawal phase. | 3 |
| Pregabalin Treatment/ No Withdrawal After finishing the pregabalin treatment phase for 8 weeks, these patients did not qualify to continue to withdrawal phase. | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Pregabalin Treatment/ Placebo Withdrawal | Pregabalin Treatment/ No Withdrawal | Total | Pregabalin Treatment/Pregabalin Withdrawal |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 5 Participants | 11 Participants | 3 Participants |
| Age, Continuous | 47.3 years STANDARD_DEVIATION 3.9 | 57.2 years STANDARD_DEVIATION 7.1 | 53.4 years STANDARD_DEVIATION 8.2 | 50.6 years STANDARD_DEVIATION 6.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 9 Participants | 3 Participants |
| Region of Enrollment United States | 3 Participants | 5 Participants | 11 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 0 / 3 | 0 / 3 | 0 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 5 |
Outcome results
Primary
Visual Analogue Score for Pain Intensity.
The primary outcome is change in visual analogue score for pain, with 0 being no pain at all and 10 being the most severe pain and a higher score meaning more pain, after 8 weeks of treatment phase and 4 weeks of randomized withdrawal phase.
Time frame: Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase
Population: Patient with idiopathic small fiber neuropathy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin Treatment/Pregabalin Withdrawal | Visual Analogue Score for Pain Intensity. | After 8 weeks of Pregabalin | 5.4 score on visual analogue score | Standard Deviation 0.8 |
| Pregabalin Treatment/Pregabalin Withdrawal | Visual Analogue Score for Pain Intensity. | Basline | 7.1 score on visual analogue score | Standard Deviation 1.4 |
| Pregabalin Treatment/Pregabalin Withdrawal | Visual Analogue Score for Pain Intensity. | After 4 weeks of Withdrawal phase | 6.1 score on visual analogue score | Standard Deviation 1.2 |
| Pregabalin Treatment/ Placebo Withdrawal | Visual Analogue Score for Pain Intensity. | After 8 weeks of Pregabalin | 5.1 score on visual analogue score | Standard Deviation 1.1 |
| Pregabalin Treatment/ Placebo Withdrawal | Visual Analogue Score for Pain Intensity. | Basline | 6.9 score on visual analogue score | Standard Deviation 1.7 |
| Pregabalin Treatment/ Placebo Withdrawal | Visual Analogue Score for Pain Intensity. | After 4 weeks of Withdrawal phase | 7.4 score on visual analogue score | Standard Deviation 1.8 |
| Pregabalin Treatment/No Withdrwal | Visual Analogue Score for Pain Intensity. | Basline | 7.3 score on visual analogue score | Standard Deviation 2.3 |
| Pregabalin Treatment/No Withdrwal | Visual Analogue Score for Pain Intensity. | After 4 weeks of Withdrawal phase | NA score on visual analogue score | — |
| Pregabalin Treatment/No Withdrwal | Visual Analogue Score for Pain Intensity. | After 8 weeks of Pregabalin | 7.6 score on visual analogue score | Standard Deviation 2.9 |
Secondary
Brief Pain Inventory (BPI sf);
Brief pain inventory is a scoring system for average pain intensity on scale of 0-10 with higher number meaning more pain.
Time frame: Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase
Population: Patients with idiopathic small fiber neuropathy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin Treatment/Pregabalin Withdrawal | Brief Pain Inventory (BPI sf); | After 8 weeks of Pregabalin | 4.9 score in brief pain inventory scale | Standard Deviation 1.1 |
| Pregabalin Treatment/Pregabalin Withdrawal | Brief Pain Inventory (BPI sf); | Basline | 6.7 score in brief pain inventory scale | Standard Deviation 0.9 |
| Pregabalin Treatment/Pregabalin Withdrawal | Brief Pain Inventory (BPI sf); | After 4 weeks of Withdrawal phase | 5.8 score in brief pain inventory scale | Standard Deviation 2.1 |
| Pregabalin Treatment/ Placebo Withdrawal | Brief Pain Inventory (BPI sf); | After 8 weeks of Pregabalin | 4.5 score in brief pain inventory scale | Standard Deviation 1.4 |
| Pregabalin Treatment/ Placebo Withdrawal | Brief Pain Inventory (BPI sf); | Basline | 6.3 score in brief pain inventory scale | Standard Deviation 1.1 |
| Pregabalin Treatment/ Placebo Withdrawal | Brief Pain Inventory (BPI sf); | After 4 weeks of Withdrawal phase | 5.6 score in brief pain inventory scale | Standard Deviation 1.9 |
| Pregabalin Treatment/No Withdrwal | Brief Pain Inventory (BPI sf); | Basline | 7.2 score in brief pain inventory scale | Standard Deviation 1.3 |
| Pregabalin Treatment/No Withdrwal | Brief Pain Inventory (BPI sf); | After 4 weeks of Withdrawal phase | NA score in brief pain inventory scale | — |
| Pregabalin Treatment/No Withdrwal | Brief Pain Inventory (BPI sf); | After 8 weeks of Pregabalin | 6.8 score in brief pain inventory scale | Standard Deviation 1.7 |
Secondary
Patient Global Impression of Change (PGIC);
patient assign a number between 1-7 to the level of improvement, 1 showing substantial improvement and 7 showing no improvement at all.
Time frame: At 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase
Population: Patients with idiopathic small fiber neuropathy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin Treatment/Pregabalin Withdrawal | Patient Global Impression of Change (PGIC); | After Withdrawal phase | 3.9 score on PGIC scale | Standard Deviation 0.7 |
| Pregabalin Treatment/Pregabalin Withdrawal | Patient Global Impression of Change (PGIC); | After 8 weeks of pregabalin | 4.1 score on PGIC scale | Standard Deviation 0.31 |
| Pregabalin Treatment/ Placebo Withdrawal | Patient Global Impression of Change (PGIC); | After Withdrawal phase | 4.2 score on PGIC scale | Standard Deviation 1.11 |
| Pregabalin Treatment/ Placebo Withdrawal | Patient Global Impression of Change (PGIC); | After 8 weeks of pregabalin | 5.4 score on PGIC scale | Standard Deviation 0.61 |
| Pregabalin Treatment/No Withdrwal | Patient Global Impression of Change (PGIC); | After 8 weeks of pregabalin | 1.8 score on PGIC scale | Standard Deviation 0.34 |
| Pregabalin Treatment/No Withdrwal | Patient Global Impression of Change (PGIC); | After Withdrawal phase | NA score on PGIC scale | — |
Secondary
Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS);
a scoring system describing sleep quality between 0-10 with 0 having no problem with sleep and 10 not being to sleep at all.
Time frame: Baseline, at 8 weeks after treatment phase and at 12 weeks for subjects completing the withdrawal phase
Population: Patients with idiopathic small fiber neuropathy
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pregabalin Treatment/Pregabalin Withdrawal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | After 8 weeks of Pregabalin | 3.1 score on Sleep Interference Rating scale | Standard Deviation 0.65 |
| Pregabalin Treatment/Pregabalin Withdrawal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | Basline | 4.5 score on Sleep Interference Rating scale | Standard Deviation 0.3 |
| Pregabalin Treatment/Pregabalin Withdrawal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | After 4 weeks of Withdrawal phase | 3.9 score on Sleep Interference Rating scale | Standard Deviation 0.71 |
| Pregabalin Treatment/ Placebo Withdrawal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | After 8 weeks of Pregabalin | 2.8 score on Sleep Interference Rating scale | Standard Deviation 1.1 |
| Pregabalin Treatment/ Placebo Withdrawal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | Basline | 5.3 score on Sleep Interference Rating scale | Standard Deviation 0.61 |
| Pregabalin Treatment/ Placebo Withdrawal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | After 4 weeks of Withdrawal phase | 4.3 score on Sleep Interference Rating scale | Standard Deviation 0.87 |
| Pregabalin Treatment/No Withdrwal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | Basline | 5.9 score on Sleep Interference Rating scale | Standard Deviation 0.7 |
| Pregabalin Treatment/No Withdrwal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | After 4 weeks of Withdrawal phase | NA score on Sleep Interference Rating scale | — |
| Pregabalin Treatment/No Withdrwal | Sleep Quality as Assessed by Daily Sleep Interference Rating Scale (SIRS); | After 8 weeks of Pregabalin | 5.1 score on Sleep Interference Rating scale | Standard Deviation 1.5 |