Ibudilast in the Treatment of Medication Overuse Headache

University of Adelaide

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Medication Overuse Headache

Treatments: Drug: Ibudilast; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01317992

U1111-1119-9613

IBU-002 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 2 patient groups, including a placebo group

Ibudilast

Experimental group

Description:

To receive ibudilast 40mg twice daily for 8 weeks.

Treatment:

Drug: Ibudilast

Placebo

Placebo Comparator group

Description:

To receive placebo twice daily for 8 weeks.

Treatment:

Drug: Placebo