Clinical trial NCT01317992: Ibudilast in the Treatment of Medication Overuse Headache
Official title: Ibudilast in the Treatment of Medication Overuse Headache: A Double-blind, Randomised, Placebo-controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Medication Overuse Headache
Keywords: Medication overuse headache
ibudilast
glia
Lead sponsor: University of Adelaide
Sponsor class: OTHER
Collaborators: name: University of South Australia
First posted: 2011-03-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if ibudilast is effective in reverting patients with medication overuse headache suffering chronic daily headache back to their original episodic headache pattern.

Detailed description: It has been established that excessive intake of medications used to treat primary headaches, particularly those containing opioids, can induce a form of secondary headache, known as medication overuse headache (MOH). Despite the significant clinical impact of this condition the mechanisms behind MOH remain poorly understood, guidelines for treatment are lacking, and relapse is common.

Recently, it has been recognised that repeated opioid exposure can facilitate pain by activating glia, the immunocompetent cells of the central nervous system, resulting in opioid-induced hyperalgesia (OIH).

The investigators hypothesise that MOH represents a form of OIH in this susceptible patient group - repeated activation of nociceptive pathways by frequent headaches interacts with the opioid induced pro-inflammatory actions of activated glia to produce chronic daily headache (CDH).

This double-blind, randomised, placebo controlled pilot study will investigate the use of ibudilast, a know attenuator of glial activation, in the treatment of medication overuse headache.

Eligibility criteria: Inclusion criteria:

* Regular use, for at least 3 months, of opioid-containing analgesics on ≥ 10 days/month
* Headache present on at least 15 days/month, for at least 2 months
* Headache developed or markedly worsened during medication overuse
* Primary indication for analgesics is headache disorder

Exclusion criteria:

* Unable to provide written informed consent
* Age \< 18 years at time of screening
* Unable to read and write in English
* Receiving tramadol regularly
* Taking triptans \> 4 days/month
* Taking opioids for reasons other than headache (e.g. other pain conditions, cough, bowel motility)
* Severe psychiatric disorders
* Other chronic pain conditions likely to interfere with qualitative sensory testing (e.g. trigeminal neuralgia, arthritis)
* Diabetic neuropathy
* Recent or current active infection, determined to be clinically significant by the Principal investigator
* Known active inflammatory diseases such as rheumatoid arthritis
* History of cerebrovascular disorder
* Recent history of significant trauma, as determined by the Principal Investigator including major surgery within the previous 2 months
* Recent history of drug or alcohol abuse
* Spinal cord injury
* Any clinically significant findings on screening blood sample results
* Current malignancy
* Known hypersensitivity to ibudilast or excipients in Pinatos® formulation
* Renal or hepatic impairment, defined as baseline GFR (as calculated by the Cockcroft-Gault equation) of \< 60 mL/min or LFTs \> 3 times the upper limit of normal
* For females of childbearing potential:

  * Pregnancy
  * Lack of adequate contraception (abstinence, double barrier method, intrauterine device, surgical sterilization (self or partner), hormonal contraceptive methods (oral, injected, or implanted)
  * Breastfeeding

Primary outcomes:
measure: Headache Index
timeFrame: 2, 4, 8, 24 weeks
Secondary outcomes:
measure: Medication frequency
timeFrame: 2, 4, 8, 24 weeks
measure: Headache frequency
timeFrame: 2, 4, 8, 24 weeks
measure: Duration of headache
timeFrame: 2, 4, 8, 24 weeks
measure: Intensity of headache
timeFrame: 2, 4, 8, 24 weeks
measure: Frequency of probable migraine attacks
timeFrame: 2, 4, 8, 24 weeks
measure: Headache related impact on quality of life
timeFrame: 2, 4, 8, 24 weeks
measure: Allodynia symptom checklist score
timeFrame: 2, 4, 8, 24 weeks
measure: Von Frey filament test
timeFrame: 2, 4, 8, 24 weeks
measure: Brush allodynia test
timeFrame: 2, 4, 8, 24 weeks
measure: Response rate
timeFrame: 2, 4, 8, 24 weeks
measure: Relapse rate
timeFrame: 2, 4, 8, 24 weeks
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: The University of Adelaide
name: Paul Rolan, MD FRACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology. 2008 Nov 25;71(22):1821-8. doi: 10.1212/01.wnl.0000335946.53860.1d.
citation: Obermann M, Katsarava Z. Management of medication-overuse headache. Expert Rev Neurother. 2007 Sep;7(9):1145-55. doi: 10.1586/14737175.7.9.1145.
citation: Hutchinson MR, Bland ST, Johnson KW, Rice KC, Maier SF, Watkins LR. Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward. ScientificWorldJournal. 2007 Nov 2;7:98-111. doi: 10.1100/tsw.2007.230.