Migraine and CVD Risk in Women

Study Overview
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Brief Summary
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The primary goal of this study is to test the effects of a high-fat, high-carbohydrate mixed meal on candidate modulators of cardiovascular disease risk (inflammation, vascular reactivity, sympathetic nervous system tone, and response to pain) in young adult women with migraine compared with healthy young women. This is study enrolling both cases (women with migraine) and controls (women without migraine), with equal numbers of normal weight and obese women in each group. Participants will undergo a telephone screening and a single day in-person study visit.

Official Title
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Mechanisms of Increased Cardiovascular Disease Risk in Women With Migraine

Conditions
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Migraine

Intervention / Treatment
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* Other: Mixed meal tolerance testing
* Other: Skin conductance & cold pressor test
* Other: Flow-mediated dilation testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (all): Female 18-35 years of age, inclusive BMI 18.5-24.9 kg/m2, inclusive BMI ≥30 kg/m2 Inclusion Criteria (cases only): Diagnosis of migraine per ICHD-3-beta (1-10 migraine days per month) Exclusion Criteria (all): Smoking (current or former) Chronic use of medications, including oral contraceptives Major medical or psychiatry illness (e.g. diabetes, fibromyalgia, major depression/anxiety) Pregnant or nursing Allergies or sensitivity to any of the ingredients of the meal Inability to fast for 10 hours and/or abstain from caffeine intake for 24 hours Treatment with antibiotics or steroids within the previous 3 months Treatment with NSAIDs within the previous 1 week Exclusion Criteria (controls only): Migraine headaches, or headaches other than tension-type headaches with a frequency of 1 or fewer days per month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are four total groups of participants, stratified according to migraine status (yes/no) and obesity status (yes/no). All undergo the same experimental phenotyping procedures.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No migraine, normal weight<br>Mixed meal tolerance testing Skin conductance & cold pressor test Flow-mediated dilation testing | Other: Mixed meal tolerance testing<br>* An intravenous catheter is placed for serial blood draws for inflammatory markers and ancillary studies. The participant consumes a test meal, and measurements are made for 4 hours.<br>Other: Skin conductance & cold pressor test<br>* Skin conductance will be monitored continuously with 2 electrodes placed on the plantar surface of the foot. To induce pain, we will use the cold pressor test. Participants submerge one hand in a bath with iced water (2-4ºC) for 2 minutes. Blood pressure and heart rate are monitored every minute starting 5 minutes before the cold pressor test and for 10 minutes after the participant withdraws the hand from the bath. This testing will be performed at baseline and post-meal.<br>Other: Flow-mediated dilation testing<br>* At baseline and post-meal, we will assess flow-mediated dilation at the brachial artery using well-validated ultrasound techniques.<br>|
| Experimental: No migraine, obese<br>Mixed meal tolerance testing Skin conductance & cold pressor test Flow-mediated dilation testing | Other: Mixed meal tolerance testing<br>* An intravenous catheter is placed for serial blood draws for inflammatory markers and ancillary studies. The participant consumes a test meal, and measurements are made for 4 hours.<br>Other: Skin conductance & cold pressor test<br>* Skin conductance will be monitored continuously with 2 electrodes placed on the plantar surface of the foot. To induce pain, we will use the cold pressor test. Participants submerge one hand in a bath with iced water (2-4ºC) for 2 minutes. Blood pressure and heart rate are monitored every minute starting 5 minutes before the cold pressor test and for 10 minutes after the participant withdraws the hand from the bath. This testing will be performed at baseline and post-meal.<br>Other: Flow-mediated dilation testing<br>* At baseline and post-meal, we will assess flow-mediated dilation at the brachial artery using well-validated ultrasound techniques.<br>|
| Experimental: Migraine, normal weight<br>Mixed meal tolerance testing Skin conductance & cold pressor test Flow-mediated dilation testing | Other: Mixed meal tolerance testing<br>* An intravenous catheter is placed for serial blood draws for inflammatory markers and ancillary studies. The participant consumes a test meal, and measurements are made for 4 hours.<br>Other: Skin conductance & cold pressor test<br>* Skin conductance will be monitored continuously with 2 electrodes placed on the plantar surface of the foot. To induce pain, we will use the cold pressor test. Participants submerge one hand in a bath with iced water (2-4ºC) for 2 minutes. Blood pressure and heart rate are monitored every minute starting 5 minutes before the cold pressor test and for 10 minutes after the participant withdraws the hand from the bath. This testing will be performed at baseline and post-meal.<br>Other: Flow-mediated dilation testing<br>* At baseline and post-meal, we will assess flow-mediated dilation at the brachial artery using well-validated ultrasound techniques.<br>|
| Experimental: Migraine, obese<br>Mixed meal tolerance testing Skin conductance & cold pressor test Flow-mediated dilation testing | Other: Mixed meal tolerance testing<br>* An intravenous catheter is placed for serial blood draws for inflammatory markers and ancillary studies. The participant consumes a test meal, and measurements are made for 4 hours.<br>Other: Skin conductance & cold pressor test<br>* Skin conductance will be monitored continuously with 2 electrodes placed on the plantar surface of the foot. To induce pain, we will use the cold pressor test. Participants submerge one hand in a bath with iced water (2-4ºC) for 2 minutes. Blood pressure and heart rate are monitored every minute starting 5 minutes before the cold pressor test and for 10 minutes after the participant withdraws the hand from the bath. This testing will be performed at baseline and post-meal.<br>Other: Flow-mediated dilation testing<br>* At baseline and post-meal, we will assess flow-mediated dilation at the brachial artery using well-validated ultrasound techniques.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LPS area under the curve (AUC) | The primary study endpoint is lipopolysaccharide (LPS) area under the curve (AUC) during MMTT. | LPS is measured at baseline every 30 minutes for 4 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flow-mediated dilation (FMD) | Vascular reactivity via brachial artery ultrasound, expressed as flow-mediated dilation (% of baseline diameter, normalized). | FMD is measured at baseline and 2.5 hours after MMTT. | 
| Sympathetic tone at rest and with painful stimulus | Sympathetic tone via skin conductance is expressed as mean skin conductance level (SCL) in microsiemens, and assessed at rest and following a pain stimulus (cold pressor test). | Sympathetic tone at rest and with painful stimulus are measured at baseline and 3 hours after MMTT. |