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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01317992




Trial ID
NCT01317992
Ethics application status
Date submitted
17/03/2011
Date registered
17/03/2011
Date last updated
4/02/2013

Titles & IDs
Public title
Ibudilast in the Treatment of Medication Overuse Headache
Scientific title
Ibudilast in the Treatment of Medication Overuse Headache: A Double-blind, Randomised, Placebo-controlled Pilot Study
Secondary ID [1] 0 0
IBU-002
Secondary ID [2] 0 0
U1111-1119-9613
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medication Overuse Headache 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ibudilast
Treatment: Drugs - Placebo

Experimental: Ibudilast - To receive ibudilast 40mg twice daily for 8 weeks.

Placebo Comparator: Placebo - To receive placebo twice daily for 8 weeks.


Treatment: Drugs: Ibudilast
Ibudilast 4 x 10 mg capsules, orally, twice daily for 8 weeks.

Treatment: Drugs: Placebo
Placebo 4 capsules, orally, twice daily for 8 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
2, 4, 8, 24 weeks
Secondary outcome [1] 0 0
Medication frequency - Defined as number of days acute headache medication taken over the previous month.
Timepoint [1] 0 0
2, 4, 8, 24 weeks
Secondary outcome [2] 0 0
Headache frequency - Defined as number of days with headache over the previous month
Timepoint [2] 0 0
2, 4, 8, 24 weeks
Secondary outcome [3] 0 0
Duration of headache - Average duration of headache in hours over previous 2 weeks
Timepoint [3] 0 0
2, 4, 8, 24 weeks
Secondary outcome [4] 0 0
Intensity of headache - Average intensity of headache assessed by numerical rating scale over previous 2 weeks
Timepoint [4] 0 0
2, 4, 8, 24 weeks
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
2, 4, 8, 24 weeks
Secondary outcome [6] 0 0
Headache related impact on quality of life - As assessed via the six-item the Headache Impact Test
Timepoint [6] 0 0
2, 4, 8, 24 weeks
Secondary outcome [7] 0 0
Allodynia symptom checklist score - Assesses presence of cutaneous allodynia during activities of daily living
Timepoint [7] 0 0
2, 4, 8, 24 weeks
Secondary outcome [8] 0 0
Von Frey filament test - To assess sensitivity to static mechanical cutaneous allodynia
Timepoint [8] 0 0
2, 4, 8, 24 weeks
Secondary outcome [9] 0 0
Brush allodynia test - To assess sensitivity to dynamic mechanical cutaneous allodynia
Timepoint [9] 0 0
2, 4, 8, 24 weeks
Secondary outcome [10] 0 0
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".
Timepoint [10] 0 0
2, 4, 8, 24 weeks
Secondary outcome [11] 0 0
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
Timepoint [11] 0 0
2, 4, 8, 24 weeks

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Pain and Anaesthesia Research Clinic, Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide

Funding & Sponsors
Primary sponsor type
Other
Name
University of Adelaide
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
University of South Australia
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01317992
Trial related presentations / publications
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.
Obermann M, Katsarava Z. Management of medication-overuse headache. Expert Rev Neurother. 2007 Sep;7(9):1145-55. Review.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Paul Rolan, MD FRACP
Address 0 0
The University of Adelaide
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Paul Rolan, MD FRACP
Address 0 0
Country 0 0
Phone 0 0
+61 8 8303 4102
Fax 0 0
Email 0 0
paul.rolan@adelaide.edu.au
Contact person for scientific queries