ANZCTR - Registration

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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

3/11/2020

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]

Nil

Universal Trial Number (UTN)

U1111-1217-5757

Trial acronym

MM2018

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Migraine

Condition category

Condition code

Neurological

Studies of the normal brain and nervous system

Neurological

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]

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]

Cerebrovascular responsiveness (CVR) to a hypercapnic stimulus, assessed with TCD ultrasound

Timepoint [1]

Week 0, 1 visit only.

Secondary outcome [1]

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]

Week 0, 1 visit only.

Secondary outcome [2]

Composite Secondary Outcome: Pulsatility and resistive indexes and resistance in the anterior cerebral circulation, assessed with a cardiovascular profiler and TCD ultrasound.

Timepoint [2]

Week 0, 1 visit only.

Secondary outcome [3]

Cognitive performance on the N-back test (administered on an iPad).

Timepoint [3]

Week 0, 1 visit only.

Secondary outcome [4]

Cerebral blood flow velocity changes during cognitive testing (CVR to cognitive stimuli), assessed with TCD ultrasound.

Timepoint [4]

Week 0, 1 visit only.

Secondary outcome [5]

5-item Migraine Disability Assessment Questionnaire (MIDAS).

Timepoint [5]

Week 0, 1 visit only.

Secondary outcome [6]

6-item Headache Impact Test (HIT-6).

Timepoint [6]

Week 0, 1 visit only.

Secondary outcome [7]

Migraine Specific Quality of Life Questionnaire MS-QOL (version 2.1).

Timepoint [7]

Week 0, 1 visit only.

Secondary outcome [8]

Gene expression, assessed by polymerase chain reaction (PCR); this is an exploratory outcome.

Timepoint [8]

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

Sex

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

Completed

Date of first participant enrolment

Anticipated

1/08/2018

Actual

23/08/2018

Date of last participant enrolment

Anticipated

30/09/2019

Actual

18/12/2019

Date of last data collection

Anticipated

30/09/2019

Actual

18/12/2019

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment postcode(s) [1]

2300 - Newcastle

Recruitment postcode(s) [2]

2308 - Newcastle University

Funding & Sponsors

Funding source category [1]

Other Collaborative groups

Name [1]

Hunter Medical Research Institute – Migraine Research Project Grant 2017

Address [1]

Lot 1, Kookaburra Circuit, New Lambton Heights NSW 2305

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Newcastle Human Research Ethics Committee

Ethics committee address [1]

Research Services, Chancellery
University of Newcastle
University Drive
Callaghan NSW 2308

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/04/2018

Approval date [1]

25/07/2018

Ethics approval number [1]

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

Prof Peter Howe

Address

Clinical Nutrition Research Centre, MS122a
University of Newcastle
School of Biomedical Sciences & Pharmacy
Callaghan NSW 2308

Country

Australia

Phone

+61 2 4921 7309

Fax

Peter.Howe@newcastle.edu.au

Contact person for public queries

Name

Peter Howe

Address

Clinical Nutrition Research Centre, MS122a
University of Newcastle
School of Biomedical Sciences & Pharmacy
Callaghan NSW 2308

Country

Australia

Phone

+61 2 4921 7309

Fax

Peter.Howe@newcastle.edu.au

Contact person for scientific queries

Name

Peter Howe

Address

Clinical Nutrition Research Centre, MS122a
University of Newcastle
School of Biomedical Sciences & Pharmacy
Callaghan NSW 2308

Country

Australia

Phone

+61 2 4921 7309

Fax

Peter.Howe@newcastle.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Cerebrovascular Function in Hormonal Migraine: An Exploratory Study.	2021	https://dx.doi.org/10.3389/fneur.2021.694980

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically