Ignite Creation Date:
2024-05-05 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00156689
Status:
COMPLETED
Last Update Posted:
2008-01-11
First Post:
2005-09-07
Brief Title:
A Study to Determine if Levetiracetam Will Assist Those Suffering From Chronic Idiopathic Axonal Polyneuropathy
Sponsor:
Vanderbilt University
Organization:
Vanderbilt University
Study Overview
Official Title:
A Pilot Study in a Double Blind Randomized Placebo-Controlled Parallel-Group 16 Week Trial Design Evaluating the Efficacy and Safety of Levetiracetam 500 mg Tablets in Bid Administration Daily Dose Ranging From 1000 mg to 3000 mg in Adults 18 Years of Ages Suffering From Chronic Idiopathic Axonal Polyneuropathy
Status:
COMPLETED
Status Verified Date:
2008-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Considering the mechanisms of action which provide efficacy in epilepsy it is hypothesized that treatment with levetiracetam will reduce the neuronal excitability involved in neuropathic pain associated with CIAP Thus there is a potential for levetiracetam to bring therapeutic benefit for the subjects because of its specific mechanism of action its safety profile and the absence of interaction with other drugs
Detailed Description:
Based on literature and expert opinion and despite the efforts made to better treat the spectrum of neuropathic pains there are still unmet needs The available treatments are not effective as monotherapy administration in the vast majority of patients and polypharmacy with several medications is often necessary Tricyclic antidepressants TCAs mainly amitriptyline are still a mainstay of treatment for painful peripheral neuropathy but at the risk of some dose-limiting adverse events which may reduce their effectiveness TCA treatment effect is inconsistent and limited by side effects In one clinical trial while about 50 of patients achieved significant or complete relief of pain 81 experienced side effects and in 71 the side effects were dose limiting TCAs can produce sedation urinary retention and orthostatic hypotension that are of particular concern in the elderly and patients with cardiovascular disease In the same study desipramine was associated with a slightly lower rate of side effects it offered only 40 of patients significant or complete relief of neuropathic pain Fluoxetine was no more effective than placebo in pain relief Max 1992 Due to the scarcity of controlled clinical trials and the inconclusive results of available trials physicians vary markedly in their suggested regimens for neuropathic pain management Beydoun 1999
Antiepileptic drugs are being used more frequently in non-epileptic indications such as neuropathic pain One of the mechanisms by which neuropathic pain occurs is related to an increased excitability of central neurons Although their precise mechanism of action in neuropathic pain remains unknown antiepileptic drugs are believed to exert their antineuralgic activity by suppressing the neuronal hyperexcitability state that characterizes neuropathic pain A small crossover trial of carbamazepine produced clinical benefit is a significant number of patients but with side effects of somnolence in 50 dizziness in 40 and rash in 6 Rull 1969 Gabapentin showed benefit over placebo in a 165-subject randomized study of painful diabetic neuropathy pain side effects were noted to be mild or moderate in most but 8 withdrew due to side effects Backonja 1998 In a placebo controlled study of lamotrigine in diabetic neuropathy there was s significant reduction in daily pain scores compared to placebo side effects were noted in about half of the treated group but were minor Eisenberg 2001 Results of treatment trials sing valproate in painful diabetic neuropathy have been variable with both positive Kochar 2004 and negative trials Otto 2004 Treatment of neuropathic pain in chronic idiopathic axonal polyneuropathy has received limited study In a single open label study or CIDP pain tiagabine produced about 30 reduction in pain severity but almost half of the patients discontinued the trial Novak 2001
Levetiracetam has been tested in two animal models of neuropathic pain Ardidd 2001 In the streptozocin diabetic rat model reactivity to a pressure on the paw was assessed and revealed that the ED50 for levetiracetam was comparable to the one observed in the epilepsy models Further hyperalgesia was dose-dependently decreased by levetiracetam On the other hand in the mononeuropathic sciatic nerve ligature model hyperalgesia was not significantly diminished Carbamazepine is effective in the sciatic nerve ligature model Animal models of neuropathic pain are considered suggestive of activity in humans but they are not directly predictive
Based on the data from the animal studies in neuropathic pain models levetiracetam has been tested in a limited basis in two human types of neurological pain painful diabetic peripheral neuropathy and sural nerve stimulation in healthy volunteers The diabetic neuropathy study was a 12-week multicenter randomized placebo-controlled parallel group study to evaluate the efficacy and safety of flexible dosing with LEV at 500 to 1500 mg bid A total of 105 subjects were included in the ITT population 52 subjects in placebo and 53 subjects in the LEV group At baseline the treatment groups were comparable with respect to demographic and other baseline characteristics There were no statistically significant or clinically meaningful treatment differences observed throughout the evaluation period relative to baseline personal communication
In the randomized double-blind crossover electrical sural nerve stimulation study pain was assessed in healthy volunteers before and 2 4 6 8 and 24 hours after 1500 mg levetiracetam or placebo was orally administered Levetiracetam significantly increased the threshold for pain detection when single electrical sural nerve stimulation was used but had no effect on temporal pain summation after repetitive sural nerve stimulation CDC It has however been demonstrated that results from one type of neuropathic pain cannot necessarily be extrapolated to other types as the negative results of the 1998 study of amitriptyline in HIV-related painful neuropathy demonstrates Beydoun 1999
A small investigator-initiated open label trial using levetiracetam in postherpetic neuralgia PHN was recently completed The study published in Neurology reported 610 patients had improvement in PHN symptomatology after a 12-week treatment with levetiracetam All 10 patients exposed had received multiple prior treatments for PHN Rowbotham 2003
Antiepileptic drugs are being used more frequently in non-epileptic indications such as neuropathic pain One of the mechanisms by which neuropathic pain occurs is related to an increased excitability of central neurons Although their precise mechanism of action in neuropathic pain remains unknown antiepileptic drugs are believed to exert their antineuralgic activity by suppressing the neuronal hyperexcitability state that characterizes neuropathic pain A small crossover trial of carbamazepine produced clinical benefit is a significant number of patients but with side effects of somnolence in 50 dizziness in 40 and rash in 6 Rull 1969 Gabapentin showed benefit over placebo in a 165-subject randomized study of painful diabetic neuropathy pain side effects were noted to be mild or moderate in most but 8 withdrew due to side effects Backonja 1998 In a placebo controlled study of lamotrigine in diabetic neuropathy there was s significant reduction in daily pain scores compared to placebo side effects were noted in about half of the treated group but were minor Eisenberg 2001 Results of treatment trials sing valproate in painful diabetic neuropathy have been variable with both positive Kochar 2004 and negative trials Otto 2004 Treatment of neuropathic pain in chronic idiopathic axonal polyneuropathy has received limited study In a single open label study or CIDP pain tiagabine produced about 30 reduction in pain severity but almost half of the patients discontinued the trial Novak 2001
Levetiracetam has been tested in two animal models of neuropathic pain Ardidd 2001 In the streptozocin diabetic rat model reactivity to a pressure on the paw was assessed and revealed that the ED50 for levetiracetam was comparable to the one observed in the epilepsy models Further hyperalgesia was dose-dependently decreased by levetiracetam On the other hand in the mononeuropathic sciatic nerve ligature model hyperalgesia was not significantly diminished Carbamazepine is effective in the sciatic nerve ligature model Animal models of neuropathic pain are considered suggestive of activity in humans but they are not directly predictive
Based on the data from the animal studies in neuropathic pain models levetiracetam has been tested in a limited basis in two human types of neurological pain painful diabetic peripheral neuropathy and sural nerve stimulation in healthy volunteers The diabetic neuropathy study was a 12-week multicenter randomized placebo-controlled parallel group study to evaluate the efficacy and safety of flexible dosing with LEV at 500 to 1500 mg bid A total of 105 subjects were included in the ITT population 52 subjects in placebo and 53 subjects in the LEV group At baseline the treatment groups were comparable with respect to demographic and other baseline characteristics There were no statistically significant or clinically meaningful treatment differences observed throughout the evaluation period relative to baseline personal communication
In the randomized double-blind crossover electrical sural nerve stimulation study pain was assessed in healthy volunteers before and 2 4 6 8 and 24 hours after 1500 mg levetiracetam or placebo was orally administered Levetiracetam significantly increased the threshold for pain detection when single electrical sural nerve stimulation was used but had no effect on temporal pain summation after repetitive sural nerve stimulation CDC It has however been demonstrated that results from one type of neuropathic pain cannot necessarily be extrapolated to other types as the negative results of the 1998 study of amitriptyline in HIV-related painful neuropathy demonstrates Beydoun 1999
A small investigator-initiated open label trial using levetiracetam in postherpetic neuralgia PHN was recently completed The study published in Neurology reported 610 patients had improvement in PHN symptomatology after a 12-week treatment with levetiracetam All 10 patients exposed had received multiple prior treatments for PHN Rowbotham 2003
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None