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Trial registered on ANZCTR


Registration number
ACTRN12616000937415
Ethics application status
Approved
Date submitted
7/07/2016
Date registered
14/07/2016
Date last updated
17/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot phase for the workplace migraine HeadAche Prevention Project (HAPPy - pilot) to investigate in a double blind randomised factorial trial whether treatment with low-dose combination blood pressure (BP) and cholesterol lowering therapy will reduce migraine compared to standard therapy and placebo.
Scientific title
An investigator initiated, multicentre, randomised double blind factorial trial to assess the effectiveness and tolerability of low-dose combination BP and cholesterol lowering therapy with placebo and standard therapy in patients with migraine.
Secondary ID [1] 289601 0
None
Universal Trial Number (UTN)
Trial acronym
HAPPy Pilot
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 299376 0
Condition category
Condition code
Other 299364 299364 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
3x3 factorial design: Participants will be randomised into a blood pressure (BP) arm and a cholesterol arm. The BP arm consists of: 1. Low-dose BP lowering combination (telmisartan 20 mg + amlodipine 2.5 mg + indapamide 1.25 mg); 2. Propranolol (160 mg/day); or 3. placebo. The cholesterol arm consists of: 1. Low-dose cholesterol lowering combination (rosuvastatin 10 mg + ezetimibe 10mg); 2. Simvastatin (20 mg/day); or 3. placebo. Medication is to be taken orally, once daily for 12 weeks. Medication usage is assessed at every follow up visit via counting remaining capsules. Any unused medication is returned at the 12 week follow up visit.
Intervention code [1] 295212 0
Treatment: Drugs
Comparator / control treatment
Placebo - commonly used excipients (to be determined) received via blinded study capsules
Control group
Placebo

Outcomes
Primary outcome [1] 298829 0
The change from baseline in mean monthly migraine headache days at 12 weeks.
Timepoint [1] 298829 0
Headache diary to be completed by participant; reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [1] 325323 0
Change from baseline in mean monthly hours with migraine
Timepoint [1] 325323 0
Headache diary to be completed by participant; reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [2] 325324 0
Proportion of subjects with at least a 50% reduction from baseline in monthly migraine headache days
Timepoint [2] 325324 0
Headache diary to be completed by participant; reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [3] 325325 0
Change from baseline in monthly migraine headache medication treatment days
Timepoint [3] 325325 0
Headache diary to be completed by participant; reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [4] 325326 0
Change from baseline in monthly lost productive work days due to migraine headache
Timepoint [4] 325326 0
Headache diary to be completed by participant; reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [5] 325327 0
Change from baseline in the number of reduced productivity work hours per month
Timepoint [5] 325327 0
Headache diary to be completed by participant; reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [6] 325328 0
Change from baseline in health-related quality of life (HRQoL)
Timepoint [6] 325328 0
Reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [7] 325329 0
Change from baseline in diastolic BP, assessed using automated sphygmomanometer
Timepoint [7] 325329 0
BP measured every 4 weeks, patient follow up: 12 weeks
Secondary outcome [8] 325330 0
Change from baseline in LDL, measured from blood sample.
Timepoint [8] 325330 0
Sample taken at 12 week follow up
Secondary outcome [9] 325331 0
Tolerability:
a. Difference between groups in potentially related side-effects (dizziness, blurred vision, syncope/collapse/fall, ankle oedema, skin rash, itching, gout, hyperkalaemia, hypokalaemia, hyponatraemia; myalgia)
b. Difference between groups in participant withdrawals from treatment
Self reported by participants during follow up visits.
Timepoint [9] 325331 0
Reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [10] 325332 0
Safety: Percentage with any serious adverse event (SAE)
Self reported by participants during follow up visits.
Timepoint [10] 325332 0
Reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [11] 325333 0
Medication adherence: Self-reported measures, pill counts
Timepoint [11] 325333 0
Reviewed every 4 weeks, patient follow up: 12 weeks
Secondary outcome [12] 325626 0
Change from baseline in systolic BP, assessed using automated sphygmomanometer
Timepoint [12] 325626 0
BP measured every 4 weeks, patient follow up: 12 weeks

Eligibility
Key inclusion criteria
Migraine headache (with or without typical aura) according to the diagnostic criteria of the International Headache Society (IHS)
* 2-14 days per month with migraine headache averaged over past 3 months (90-days), as self-reported by subject
* Migraine symptoms must have been present for greater than or equal to 1 year prior to enrolment in the study.
* Onset of migraine symptoms must have occurred before the age of 50 years
* Adults between 18 and 65 years
* Office SBP greater than or equal to 130mmHg and DBP greater than or equal 80 mmHg
* No definite contraindications to any of the study medications at the doses used in this trial. (Subjects can be taking other preventive and therapeutic medications as long as they do not contraindicate study medication. Patients will not be eligible if they are taking medications from the same class as the study treatments)
* Is medically stable as determined by the Study Investigator
* If taking any concomitant migraine preventative medication(s), is on a stabilised dosage at the discretion of the Investigator
* Is willing to stay on current migraine preventative medication(s) for the duration of the study
* Is able to take oral medication, adhere to the medication regimens, and perform study procedures over the study duration.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Contraindication to any of telmisartan, amlodipine, indapamide, rosuvastatin, ezetimibe, simvastatin or propranolol
* Concomitantly taking an angiotensin receptor blocker, angiotensin converting enzyme inhibitor, calcium channel blocker, diuretic or statin.
* Definite indication to any one or more of the study medications
* Subject has history of cluster headaches
* Subject who exclusively has migraine aura without headache, migraine with brainstem aura, hemiplegic migraine or chronic migraine
* Medication overuse headaches according to International Headache Society criteria
* Female patients who are pregnant, nursing, or those not using adequate birth control, if capable of bearing children.
* Chronic medical illnesses (e.g. lupus) that could potentially affect frequency of headache as determined by the Study Investigator
* Alcohol or substance abuse within the last year
* Any concurrent medical or psychiatric condition which, in the investigator's judgment, may interfere with study conduct or which contraindicates participation
* Abnormal creatinine, urea or electrolytes on screening.
* Inability to provide informed consent.
* Participation in a concurrent interventional medical investigation or clinical trial. Subjects in observational, natural history and/or epidemiological studies not involving an intervention are eligible.

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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features

Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Pilot study timelines were revised
Date of first participant enrolment
Anticipated
1/08/2016
Actual
6/03/2017
Date of last participant enrolment
Anticipated
Actual
1/03/2018
Date of last data collection
Anticipated
19/07/2018
Actual
22/06/2018
Sample size
Target
180
Accrual to date
Final
44
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 8851 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 8852 0
Liverpool Hospital - Liverpool
Recruitment postcode(s) [1] 17077 0
2050 - Camperdown
Recruitment postcode(s) [2] 17078 0
2170 - Liverpool

Funding & Sponsors
Funding source category [1] 294001 0
Other
Name [1] 294001 0
The George Institute for Global Health
Country [1] 294001 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
Level 10, King George V Building
Missenden Road
Camperdown, NSW 2050
Country
Australia
Secondary sponsor category [1] 292821 0
None
Name [1] 292821 0
Address [1] 292821 0
Country [1] 292821 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295414 0
Sydney Local Health District Ethics Review Committee (Royal Prince Alfred Hospital (RPAH) Zone)
Ethics committee address [1] 295414 0
Royal Prince Alfred Hospital
Missenden Road, CAMPERDOWN, NSW, 2050
Ethics committee country [1] 295414 0
Australia
Date submitted for ethics approval [1] 295414 0
09/11/2015
Approval date [1] 295414 0
10/05/2016
Ethics approval number [1] 295414 0
15/RPAH/554

Summary
Brief summary
Recurrent headache is a common, disabling condition affecting millions of Australians. Migraine is a major cause of burden of disease ranking up to 6th highest cause of major disability worldwide. Globally, an estimated 0.8 billion people suffer from migraine.
Headaches are a leading cause of lost work productivity, with reduced performance rather than absence from work being the main cause of lost productive time.
There would therefore be considerable value in a simple, highly tolerable preventive therapy for the large number of people suffering from frequent migraine. In the pilot phase of this trial, the key objectives are to determine the recruitment, adherence, BP and LDL differences and assess the safety of the inventions consisting of a low-dose BP lowering combination and/or a low-dose statin in participants who experience frequent migraine.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 67162 0
Prof Craig Anderson
Address 67162 0
The George Institute for Global Health, Australia
Level 10, King George V Building, 83-117 Missenden Rd, Camperdown NSW 2050
Country 67162 0
Australia
Phone 67162 0
+61 2 8052 4521
Fax 67162 0
Email 67162 0
[email protected]
Contact person for public queries
Name 67163 0
Ruth Freed
Address 67163 0
The George Institute for Global Health, Australia
Level 10, King George V Building, 83-117 Missenden Rd, Camperdown NSW 2050
Country 67163 0
Australia
Phone 67163 0
+61 2 8052 4522
Fax 67163 0
Email 67163 0
[email protected]
Contact person for scientific queries
Name 67164 0
Cheryl Carcel
Address 67164 0
The George Institute for Global Health, Australia
Level 10, King George V Building, 83-117 Missenden Rd, Camperdown NSW 2050
Country 67164 0
Australia
Phone 67164 0
+61 2 8052 4508
Fax 67164 0
Email 67164 0
[email protected]

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