A Phase 2/3 interventional study of phenytoin cream and Placebo cream in Chronic Idiopathic Axonal Polyneuropathy, sponsored by David J. Kopsky. Completed at 1 site in Netherlands. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2023-06-28.
Sponsored by David J. Kopsky · Phase 2/3, Interventional, and Treatment
Objectives: The main objective is to evaluate the efficacy and safety of phenytoin cream in patients with neuropathic pain due to chronic idiopathic axonal polyneuropathy (CIAP). The second objective is to determine the predictive value of a double-blind placebo-controlled response test (DOBRET) to identify sustained responders.
Study design: This is a 6-week enrichment randomized double-blind, placebo-controlled cross-over trial evaluating phenytoin cream in 84 participants with painful CIAP, whereafter an open label extension phase is offered with phenytoin 20 percent cream for up to one year.
At baseline a DOBRET with phenytoin 10 percent and placebo cream will be performed in each study participant to stratify participants according to their response to the DOBRET before entering the double-blind cross-over phase. DOBRET positive participants are those who experience at least two points pain reduction on the 11-point numerical rating scale (NRS) on the phenytoin 10 percent cream applied area within 30 minutes and at least one-point difference in pain reduction on the NRS between phenytoin 10 percent and placebo cream applied area, in favour of the former.
Participants will receive three treatments in a double blind fashion and in a randomized order: phenytoin 10 percent, phenytoin 20 percent and placebo cream. The duration of each treatment period is two weeks. Participants will cross-over two times to each of the other treatments. The study does not have wash-out periods between treatments, because the mean duration of analgesic effect after an application is expected to be less than nine hours. A blood sample will be collected at the end of the second week of the first treatment period to test for phenytoin plasma levels.
Study population: The investigators aim to include 84 participants, age 40 years or older, who have been diagnoses with painful CIAP at the University Medical Center Utrecht and fulfil the inclusion criteria and have given written informed consent.
Interventions: Phenytoin cream in concentrations of 10 percent and 20 percent cream compared to placebo cream.
Primary endpoint: Change in pain intensity measured on the NRS between baseline and week 2 for phenytoin 20% cream versus placebo cream.
256 studies on the registry are indexed under Polyneuropathies; 50 are open to participants now.
This study's enrollment of 81 is close to the median of 75 across 162 interventional studies indexed under Polyneuropathies.
Browse Polyneuropathies studies →This is the only study on the registry with David J. Kopsky as lead sponsor.
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Exclusion Criteria:
Phenytoin 10 percent cream, 2 to 4 times daily application, 2 weeks long
Drug: phenytoin cream
Phenytoin 20 percent cream, 2 to 4 times daily application, 2 weeks long
Drug: phenytoin cream
Placebo cream, 2 to 4 times daily application, 2 weeks long
Other: Placebo cream
Phenytoin cream to be applied on the neuropathic pain area
Placebo cream to be applied on the neuropathic pain area
Change in mean pain intensity measured on the 11-point numerical rating scale (NRS) between baseline and week 2 for phenytoin 20% cream versus placebo cream.
0 = no pain, 10 = worst imaginable pain. The bigger the mean change, the better the outcome
Time frame: Mean baseline vs. mean of second week of each intervention
Change in mean pain intensity from baseline 11-point numerical rating scale (NRS) to the mean NRS in the second week in double-blind response test in positive and negative participants and all participants combined
0 = no pain, 10 = worst imaginable pain. The bigger the mean change, the better the outcome
Time frame: Mean baseline vs. mean of second week of each intervention
Change of EuroQol (EQ5-5D-5L) from baseline to the end of the second week of each treatment period
EQ5-5D-5L consists of 5 quality of life questions assessed on a 5 point scale: the lower the score, the better quality of life. Furthermore, a visual analogue scale from 0 to 100 is included. The higher the score, the better quality of life.
Time frame: Baseline vs. end of second week of each intervention
Change of Neuropathic Pain Symptom Inventory (NPSI) from baseline to the end of the second week of each treatment period
The NPSI consists of 10 neuropathic pain descriptors on the NRS, and 2 items assessing the duration of spontaneous ongoing and paroxysmal pain. The lower the score, the less pain.
Time frame: Baseline vs. end of second week of each intervention
Change of subscales of the Brief Pain Inventory (sBPI) from baseline to the end of the second week of each treatment period
The sBPI consists of 7 quality of life questions, assessed on the NRS. The lower the score, the better quality of life.
Time frame: Baseline vs. end of second week of each intervention
Change of the 3 worst pain characteristics from baseline to the end of the second week of each treatment period
The 3 worst pain characteristics are scored on the NRS. The lower the score, the less pain.
Time frame: Baseline vs. end of second week of each intervention
Change of Patient Global Impression of Change Scale (PGIC) from baseline to the end of the second week of each treatment period
The PGIC is a 7-point satisfaction scale. The lower the score, the better.
Time frame: Baseline vs. end of second week of each intervention
30 percent and 50 percent improvement or more on the NRS compared to placebo within one patient
Time frame: Baseline vs. end of second week of each intervention
Time of carry-over effects after a treatment period
Time frame: First week of each intervention
Onset of analgesic effect after application
The onset of analgesic effect will be noted in minutes.
Time frame: At the end of second week of each intervention
Duration of analgesic effect
The duration of analgesic effect will be noted in hours.
Time frame: At the end of second week of each intervention
Daily number of cream applications
Time frame: At the end of second week of each intervention
Percentage of analgesic effect as rated by the participant
The participant will be asked about the percentage of pain reduction at the end of the second week of each intervention. The higher, the better.
Time frame: At the end of second week of each intervention.
Local and/or systemic side effects
At each visit and telephone call participants will be asked about possibly occurring side effects.
Time frame: During the 6 weeks of double-blind phase and 1 year open phase
Detection of phenytoin in plasma
Two hours after last application phenytoin plasma level will be evaluated
Time frame: At the end of second week of first treatment period
Predictive value of DOBRET
Correlation with DOBRET response and mean pain reduction while using phenytoin 10 percent or 20 percent cream. The stronger the correlation, the more predictive the DOBRET is.
Time frame: Baseline vs. mean of second week of each intervention
Use of escape pain medication
The daily amount of acetaminophen and/or non-steroid anti-inflammatory drugs
Time frame: During the 6 weeks of double-blind phase and 1 year open phase
Plan to share: No
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