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Trial registered on ANZCTR


Registration number
ACTRN12618001230246
Ethics application status
Approved
Date submitted
17/07/2018
Date registered
23/07/2018
Date last updated
2/07/2019
Date data sharing statement initially provided
2/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Relationships between cerebrovascular function and the incidence and severity of headache in premenopausal women
Scientific title
Relationships between cerebrovascular function and the incidence and severity of headache in premenopausal women
Secondary ID [1] 295581 0
Nil
Universal Trial Number (UTN)
U1111-1217-5757
Trial acronym
MM2018
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 308867 0
Condition category
Condition code
Neurological 307790 307790 0 0
Studies of the normal brain and nervous system
Neurological 307821 307821 0 0
Other neurological disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
70 premenopausal women will be allocated to either the menstrual migraine group or the control group. They will attend our clinic for one visit only. We will measure blood pressure and arterial compliance, then fit a headpiece with transcranial doppler (TCD) ultrasound probes to measure blood flow in the brain; this will be monitored while participants perform a hypercapnia test and the N-back test. Participants will complete three questionnaires (MIDAS, HIT-6 and MS-QOL). A blood sample will be obtained to explore gene expression. The visit will take approximately two and a half hours.
Women will be included in the menstrual migraine group if they suffer from migraine/headache +/- 3 days from their period and/or ovulation (mid-cycle) in the previous three menstrual cycles, lasting 4-72 hours with at least two of these characteristics: unilateral location, pulsating or throbbing pain, pain of at least moderate intensity, or aggravated by or causing avoidance of physical activity (walking/stair climbing). They should be free from headache attacks at other times of the cycle.
Intervention code [1] 301879 0
Early Detection / Screening
Comparator / control treatment
Participants will be allocated to either the menstrual migraine group or the control group.
Control group
Active

Outcomes
Primary outcome [1] 306775 0
Cerebrovascular responsiveness (CVR) to a hypercapnic stimulus, assessed with TCD ultrasound
Timepoint [1] 306775 0
Week 0, 1 visit only.
Secondary outcome [1] 349558 0
Composite Secondary Outcome: Clinic systolic blood pressure (BP), diastolic BP, heart rate (HR), large and small artery elasticity indices, assessed using a Cardiovascular Profiler.
Timepoint [1] 349558 0
Week 0, 1 visit only.
Secondary outcome [2] 349562 0
Composite Secondary Outcome: Pulsatility and resistive indexes and resistance in the anterior cerebral circulation, assessed with a cardiovascular profiler and TCD ultrasound.
Timepoint [2] 349562 0
Week 0, 1 visit only.
Secondary outcome [3] 349563 0
Cognitive performance on the N-back test (administered on an iPad).
Timepoint [3] 349563 0
Week 0, 1 visit only.
Secondary outcome [4] 349566 0
Cerebral blood flow velocity changes during cognitive testing (CVR to cognitive stimuli), assessed with TCD ultrasound.
Timepoint [4] 349566 0
Week 0, 1 visit only.
Secondary outcome [5] 349567 0
5-item Migraine Disability Assessment Questionnaire (MIDAS).
Timepoint [5] 349567 0
Week 0, 1 visit only.
Secondary outcome [6] 349569 0
6-item Headache Impact Test (HIT-6).
Timepoint [6] 349569 0
Week 0, 1 visit only.
Secondary outcome [7] 349571 0
Migraine Specific Quality of Life Questionnaire MS-QOL (version 2.1).
Timepoint [7] 349571 0
Week 0, 1 visit only.
Secondary outcome [8] 349572 0
Gene expression, assessed by polymerase chain reaction (PCR); this is an exploratory outcome.
Timepoint [8] 349572 0
Week 0, 1 visit only.

Eligibility
Key inclusion criteria
Women between age 25 and menopause (> 6 months cessation of menses)
Blood pressure <160/100mmHg (determined at screening visit)
For migraine group: Suffer from migraine/headache +/- 3 days from their period and/or ovulation (mid-cycle) in the previous three menstrual cycles, lasting 4-72 hours with at least two of these characteristics: unilateral location, pulsating or throbbing pain, pain of at least moderate intensity, or aggravated by or causing avoidance of physical activity (walking/ stair climbing). They should be free from headache attacks at other times of the cycle.
Minimum age
25 Years
Maximum age
60 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Not fluent in reading and writing in English.
No detectable transcranial Doppler (TCD) ultrasound signal in the middle cerebral artery on either side.
TCD blood flow velocity >185 cm/s
Liver or kidney disease
Hysterectomy
Malignant cancer
Insulin-dependent diabetes
Fibromyalgia
Excessive alcohol intake (>15 drinks per week)
Pregnancy or breastfeeding
Major depression
Neurological conditions including stroke, TIA, major depression, multiple sclerosis, epilepsy, Chiari malformation, Parkinson’s disease or dementia or mild cognitive impairment.
Unwilling to provide a blood sample
Smoker
History of using Botulinum toxin or neuromodulation devices for treatment of headaches.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
An independent t-test will be used to compare group differences (migraineur vs. non-migraineur) in basal cerebral hemodynamics (mean BFV, PI, RI and cerebrovascular resistance index), CVR to hypercapnia and CVR to N-back test (neurovascular coupling capacity). The associations between cerebrovascular function, headache characteristics such as frequency, severity, average duration of each attack will be examined using linear regression and Bayesian analyses. Correlations between polymorphisms associated with migraine susceptibility (identified by genotypic profiling) and cerebrovascular function will be determined by regression analysis. If possible, we will also determine whether use of oral contraception is associated with headache severity, frequency or duration and impairment of cerebrovascular function using Wald’s test. Estradiol levels may be included as a covariate in the analysis. Adjustment for multiple comparisons will also be made.

Recruitment
Recruitment status
Recruiting
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)
NSW
Recruitment postcode(s) [1] 23465 0
2300 - Newcastle
Recruitment postcode(s) [2] 23466 0
2308 - Newcastle University

Funding & Sponsors
Funding source category [1] 300158 0
Other Collaborative groups
Name [1] 300158 0
Hunter Medical Research Institute – Migraine Research Project Grant 2017
Address [1] 300158 0
Lot 1, Kookaburra Circuit, New Lambton Heights NSW 2305
Country [1] 300158 0
Australia
Primary sponsor type
University
Name
University of Newcastle
Address
University of Newcastle
Faculty of Health and Medicine
School of Biomedical Sciences & Pharmacy
Clinical Nutrition Research Centre
Callaghan, New South Wales 2308
Australia
Country
Australia
Secondary sponsor category [1] 299566 0
None
Name [1] 299566 0
Address [1] 299566 0
Country [1] 299566 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300989 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [1] 300989 0
Research Services, Chancellery
University of Newcastle
University Drive
Callaghan NSW 2308
Ethics committee country [1] 300989 0
Australia
Date submitted for ethics approval [1] 300989 0
17/04/2018
Approval date [1] 300989 0
25/07/2018
Ethics approval number [1] 300989 0

Summary
Brief summary
Migraine is an episodic primary headache disorder, affecting 10% of adults with varying degree of disability that can interfere with daily living. The prevalence of migraine is 2 to 3 times greater in women than in men, particularly during reproductive years; peaking between 30 and 39 years of age and a second peak around 50 years old (onset of menopause). It is estimated that migraine attacks related to menstruation occur in 35-51% of women and are associated with the fall of estrogen levels (~2 days before menses) and may continue for a few more days until estrogen levels rise again.

There is growing appreciation of the link between migraine and heightened risk of vascular diseases, particularly for stroke. In fact, studies have shown that women with migraine, especially with aura, are at twice the risk for ischemic stroke. We want to characterise any circulatory abnormalities in the brain in women who suffer from menstrual migraine.

In this study, we will measure the flow of blood in the brain in premenopausal women and compare those who suffer from menstrual migraine with those who are not susceptible. We will also explore the role of blood pressure, differences in gene expression, stiffness of blood vessels, and the effects of menstrual migraine on quality of life and mental performance.

We aim to see whether abnormalities of blood flow in the brain may predispose women to menstrual migraine and to see whether these abnormalities are associated with differences in gene expression between those who suffer from menstrual migraine and those who are not susceptible. This information will help us to design more effective interventions to counteract migraine.
Trial website
Trial related presentations / publications
Public notes
Recruitment is not restricted to the Newcastle and Callaghan postcodes listed, it is open to all postcodes in the Hunter Region and beyond.

Contacts
Principal investigator
Name 85530 0
Prof Peter Howe
Address 85530 0
Clinical Nutrition Research Centre, MS122a
University of Newcastle
School of Biomedical Sciences & Pharmacy
Callaghan NSW 2308
Country 85530 0
Australia
Phone 85530 0
+61 2 4921 7309
Fax 85530 0
Email 85530 0
Peter.Howe@newcastle.edu.au
Contact person for public queries
Name 85531 0
Prof Peter Howe
Address 85531 0
Clinical Nutrition Research Centre, MS122a
University of Newcastle
School of Biomedical Sciences & Pharmacy
Callaghan NSW 2308
Country 85531 0
Australia
Phone 85531 0
+61 2 4921 7309
Fax 85531 0
Email 85531 0
Peter.Howe@newcastle.edu.au
Contact person for scientific queries
Name 85532 0
Prof Peter Howe
Address 85532 0
Clinical Nutrition Research Centre, MS122a
University of Newcastle
School of Biomedical Sciences & Pharmacy
Callaghan NSW 2308
Country 85532 0
Australia
Phone 85532 0
+61 2 4921 7309
Fax 85532 0
Email 85532 0
Peter.Howe@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results