Ibudilast in the Treatment of Medication Overuse Headache

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01317992
Recruitment Status : Unknown
Verified February 2013 by Prof Paul Rolan, University of Adelaide.
Recruitment status was:  Recruiting
First Posted : March 18, 2011
Last Update Posted : February 6, 2013
University of South Australia
Information provided by (Responsible Party):
Prof Paul Rolan, University of Adelaide

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.

Condition or disease Intervention/treatment Phase
Medication Overuse Headache Drug: Ibudilast Drug: Placebo Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Ibudilast in the Treatment of Medication Overuse Headache: A Double-blind, Randomised, Placebo-controlled Pilot Study
Study Start Date : April 2011
Estimated Primary Completion Date : June 2013
Estimated Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Ibudilast
To receive ibudilast 40mg twice daily for 8 weeks.
Drug: Ibudilast
Ibudilast 4 x 10 mg capsules, orally, twice daily for 8 weeks.

Placebo Comparator: Placebo
To receive placebo twice daily for 8 weeks.
Drug: Placebo
Placebo 4 capsules, orally, twice daily for 8 weeks.

Primary Outcome Measures :
  1. Headache Index [ Time Frame: 2, 4, 8, 24 weeks ]
    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.

Secondary Outcome Measures :
  1. Medication frequency [ Time Frame: 2, 4, 8, 24 weeks ]
    Defined as number of days acute headache medication taken over the previous month.

  2. Headache frequency [ Time Frame: 2, 4, 8, 24 weeks ]
    Defined as number of days with headache over the previous month

  3. Duration of headache [ Time Frame: 2, 4, 8, 24 weeks ]
    Average duration of headache in hours over previous 2 weeks

  4. Intensity of headache [ Time Frame: 2, 4, 8, 24 weeks ]
    Average intensity of headache assessed by numerical rating scale over previous 2 weeks

  5. Frequency of probable migraine attacks [ Time Frame: 2, 4, 8, 24 weeks ]
    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

  6. Headache related impact on quality of life [ Time Frame: 2, 4, 8, 24 weeks ]
    As assessed via the six-item the Headache Impact Test

  7. Allodynia symptom checklist score [ Time Frame: 2, 4, 8, 24 weeks ]
    Assesses presence of cutaneous allodynia during activities of daily living

  8. Von Frey filament test [ Time Frame: 2, 4, 8, 24 weeks ]
    To assess sensitivity to static mechanical cutaneous allodynia

  9. Brush allodynia test [ Time Frame: 2, 4, 8, 24 weeks ]
    To assess sensitivity to dynamic mechanical cutaneous allodynia

  10. Response rate [ Time Frame: 2, 4, 8, 24 weeks ]
    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".

  11. Relapse rate [ Time Frame: 2, 4, 8, 24 weeks ]
    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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01317992

Contact: Paul Rolan, MD FRACP +61 8 8303 4102

Australia, South Australia
Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Sponsors and Collaborators
University of Adelaide
University of South Australia
Principal Investigator: Paul Rolan, MD FRACP The University of Adelaide

Additional Information:
Responsible Party: Prof Paul Rolan, Professor Paul Rolan, University of Adelaide Identifier: NCT01317992     History of Changes
Other Study ID Numbers: U1111-1119-9613
IBU-002 ( Other Identifier: The University of Adelaide )
First Posted: March 18, 2011    Key Record Dates
Last Update Posted: February 6, 2013
Last Verified: February 2013

Keywords provided by Prof Paul Rolan, University of Adelaide:
Medication overuse headache

Additional relevant MeSH terms:
Headache Disorders, Secondary
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Vasodilator Agents