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Ibudilast in the Treatment of Medication Overuse Headache

Primary Purpose

Medication Overuse Headache

Status
Unknown status
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Ibudilast
Placebo
Sponsored by
University of Adelaide
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Medication Overuse Headache focused on measuring Medication overuse headache, ibudilast, glia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Pain and Anaesthesia Research Clinic, Royal Adelaide HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ibudilast

Placebo

Arm Description

To receive ibudilast 40mg twice daily for 8 weeks.

To receive placebo twice daily for 8 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Medication frequency
Defined as number of days acute headache medication taken over the previous month.
Headache frequency
Defined as number of days with headache over the previous month
Duration of headache
Average duration of headache in hours over previous 2 weeks
Intensity of headache
Average intensity of headache assessed by numerical rating scale over previous 2 weeks
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
Headache related impact on quality of life
As assessed via the six-item the Headache Impact Test
Allodynia symptom checklist score
Assesses presence of cutaneous allodynia during activities of daily living
Von Frey filament test
To assess sensitivity to static mechanical cutaneous allodynia
Brush allodynia test
To assess sensitivity to dynamic mechanical cutaneous allodynia
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".
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

Full Information

First Posted
March 17, 2011
Last Updated
February 4, 2013
Sponsor
University of Adelaide
Collaborators
University of South Australia
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1. Study Identification

Unique Protocol Identification Number
NCT01317992
Brief Title
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

2. Study Status

Record Verification Date
February 2013
Overall Recruitment Status
Unknown status
Study Start Date
April 2011 (undefined)
Primary Completion Date
June 2013 (Anticipated)
Study Completion Date
August 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Adelaide
Collaborators
University of South Australia

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Medication Overuse Headache
Keywords
Medication overuse headache, ibudilast, glia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ibudilast
Arm Type
Experimental
Arm Description
To receive ibudilast 40mg twice daily for 8 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
To receive placebo twice daily for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Ibudilast
Intervention Description
Ibudilast 4 x 10 mg capsules, orally, twice daily for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 4 capsules, orally, twice daily for 8 weeks.
Primary Outcome Measure Information:
Title
Headache Index
Description
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.
Time Frame
2, 4, 8, 24 weeks
Secondary Outcome Measure Information:
Title
Medication frequency
Description
Defined as number of days acute headache medication taken over the previous month.
Time Frame
2, 4, 8, 24 weeks
Title
Headache frequency
Description
Defined as number of days with headache over the previous month
Time Frame
2, 4, 8, 24 weeks
Title
Duration of headache
Description
Average duration of headache in hours over previous 2 weeks
Time Frame
2, 4, 8, 24 weeks
Title
Intensity of headache
Description
Average intensity of headache assessed by numerical rating scale over previous 2 weeks
Time Frame
2, 4, 8, 24 weeks
Title
Frequency of probable migraine attacks
Description
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
Time Frame
2, 4, 8, 24 weeks
Title
Headache related impact on quality of life
Description
As assessed via the six-item the Headache Impact Test
Time Frame
2, 4, 8, 24 weeks
Title
Allodynia symptom checklist score
Description
Assesses presence of cutaneous allodynia during activities of daily living
Time Frame
2, 4, 8, 24 weeks
Title
Von Frey filament test
Description
To assess sensitivity to static mechanical cutaneous allodynia
Time Frame
2, 4, 8, 24 weeks
Title
Brush allodynia test
Description
To assess sensitivity to dynamic mechanical cutaneous allodynia
Time Frame
2, 4, 8, 24 weeks
Title
Response rate
Description
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".
Time Frame
2, 4, 8, 24 weeks
Title
Relapse rate
Description
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
Time Frame
2, 4, 8, 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paul Rolan, MD FRACP
Phone
+61 8 8303 4102
Email
paul.rolan@adelaide.edu.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Rolan, MD FRACP
Organizational Affiliation
The University of Adelaide
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting

12. IPD Sharing Statement

Citations:
PubMed Identifier
19029522
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.
Results Reference
background
PubMed Identifier
17868013
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.
Results Reference
background
PubMed Identifier
17982582
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.
Results Reference
background
Links:
URL
http://www.adelaide.edu.au/painresearch/
Description
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