Ibudilast in the Treatment of Medication Overuse Headache

Medication Overuse Headache Clinical Trial

Official title:

Ibudilast in the Treatment of Medication Overuse Headache: A Double-blind, Randomised, Placebo-controlled Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01317992
• Other study ID #: U1111-1119-9613
• Secondary ID: IBU-002
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: March 17, 2011
• Last updated: February 4, 2013
• Start date: April 2011
• Est. completion date: August 2013

Study information

• Verified date: February 2013
• Source: University of Adelaide
• Contact: Paul Rolan, MD FRACP
• Phone: +61 8 8303 4102
• Email: paul.rolan[@]adelaide.edu.au
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: August 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Headache
• Headache Disorders, Secondary
• Medication Overuse Headache

Intervention

Drug:
• Ibudilast
Ibudilast 4 x 10 mg capsules, orally, twice daily for 8 weeks.
• Placebo
Placebo 4 capsules, orally, twice daily for 8 weeks.

Locations

Country	Name	City	State
Australia	Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital	Adelaide	South Australia

Sponsors (2)

Lead Sponsor	Collaborator
University of Adelaide	University of South Australia

Country where clinical trial is conducted

Australia, 

References & Publications (3)

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. Review. — View 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. Review. — View Citation

Obermann M, Katsarava Z. Management of medication-overuse headache. Expert Rev Neurother. 2007 Sep;7(9):1145-55. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Headache Index	Headache Index as calculated by the summation of headache duration (hours) X headache intensity (11-point numerical rating scale), over the final two weeks of treatment.	2, 4, 8, 24 weeks	No
Secondary	Medication frequency	Defined as number of days acute headache medication taken over the previous month.	2, 4, 8, 24 weeks	No
Secondary	Headache frequency	Defined as number of days with headache over the previous month	2, 4, 8, 24 weeks	No
Secondary	Duration of headache	Average duration of headache in hours over previous 2 weeks	2, 4, 8, 24 weeks	No
Secondary	Intensity of headache	Average intensity of headache assessed by numerical rating scale over previous 2 weeks	2, 4, 8, 24 weeks	No
Secondary	Frequency of probable migraine attacks	Defined as number of probable migraine attacks (using International Classification of Headache Disorders, second edition, criteria for diagnosis of migraine/migraine with aura) over previous month	2, 4, 8, 24 weeks	No
Secondary	Headache related impact on quality of life	As assessed via the six-item the Headache Impact Test	2, 4, 8, 24 weeks	No
Secondary	Allodynia symptom checklist score	Assesses presence of cutaneous allodynia during activities of daily living	2, 4, 8, 24 weeks	No
Secondary	Von Frey filament test	To assess sensitivity to static mechanical cutaneous allodynia	2, 4, 8, 24 weeks	No
Secondary	Brush allodynia test	To assess sensitivity to dynamic mechanical cutaneous allodynia	2, 4, 8, 24 weeks	No
Secondary	Response rate	Response defined as = 30% reduction in headache days/month or headache index from baseline. Expressed as percentage of patients who saw a = 30% reduction in headache index after ibudilast treatment (at week 8) and NNT, number of patients treated to see 1 patient "respond".	2, 4, 8, 24 weeks	No
Secondary	Relapse rate	Expressed as the percentage of patients who were initially classed as responders (at weeks 8) who no longer meet the criteria for responders at 6 months	2, 4, 8, 24 weeks	No

External Links

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