Investigation of Vascular Inflammation in Migraine Without Aura Using Molecular Nano-imaging and Black Blood Imaging MRI
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Change in USPIO uptake during attacks of unilateral migraine without aura compared to baseline
研究概览
简要总结
The investigators aim to investigate inflammation of cranial and meningeal arteries during pharmacologically induced migraine attacks, using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and black blood imaging (BBI) MRI.
详细描述
Migraine is the most common neurological disorder, ranked as the 7th most debilitating disease worldwide by the WHO. While much research has been and continues to be conducted to illuminate the enigma of migraine pathophysiology, key aspects still remain a conundrum. Specifically, the process of headache generation is perhaps the most complex and debated part of migraine pathophysiology. The vascular hypothesis of migraine has traditionally focused on the simple dilatation of cranial arteries. However, a possible contribution of perivascular pain sensitive structures should also be considered, as aseptic inflammation of the arterial walls and perivascular space may activate afferent nerve endings. Interestingly, giant cell arteritis caused by aseptic arterial wall inflammation may present clinically as localized headache with migraine-like features (i.e. throbbing pain, localized in the temporal region, and allodynia).
The primary trigeminal nociceptor is the first integral part of the headache-generating pathway. Animal models of migraine have suggested that activation and sensitization of perivascular trigeminal nociceptors caused by inflammatory substances may explain head pain in migraine. However, there is no human evidence to date to suggest perivascular and arterial wall inflammation as a source of pain in migraine.
The investigators hypothesize that unilateral migraine without aura is associated with ipsilateral inflammation of the cranial arteries and meninges. The investigators also suggest that sumatriptan inhibits this perivascular inflammation. To test the hypotheses the investigators will perform MRI scans on subjects with provoked migraine attacks, using two different methods to visualize perivascular inflammation: USPIO-MRI, using iron-oxide nanoparticles as contrast agent, and BBI MRI.
To pharmacologically induce migraine headache in the study subjects, the investigators will use the drug cilostazol, which is a phosphodiesterase 3 inhibitor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Subject has migraine without aura according to criteria of the International Headache Society (IHS)
- •Subject has unilateral migraine 70% of the time
- •Migraine can be pharmacologically provoked in the subject using cilostazol.
- •Subject is on birth control
- •Subject has no other medical history
排除标准
- •Subject suffers from bilateral migraine
- •Subject suffers from migraine with aura
- •Subject suffers from other primary headaches as specified by IHS criteria
- •Pregnant or breast feeding subjects
- •Subjects with contraindications for undergoing MRI scans
- •Any known drug allergy
- •Any signs or disorders of iron overload, including but not limited to hemosiderosis and porphyria cutanea tarda
研究组 & 干预措施
Vascular inflammation
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan, undergo pharmacological induction of a migraine attack, and subsequently are MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI ).
干预措施: Feraheme (Drug)
Vascular inflammation
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan, undergo pharmacological induction of a migraine attack, and subsequently are MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI ).
干预措施: Cilostazol (Drug)
Vascular inflammation
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan, undergo pharmacological induction of a migraine attack, and subsequently are MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI ).
干预措施: USPIO-MRI (Other)
Vascular inflammation
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan, undergo pharmacological induction of a migraine attack, and subsequently are MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI ).
干预措施: BBI-MRI (Other)
Effect of sumatriptan
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan and then undergo pharmacological induction of a migraine attack. Sumatriptan is given and subjects subsequently undergo MRI scans prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI).
干预措施: Feraheme (Drug)
Effect of sumatriptan
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan and then undergo pharmacological induction of a migraine attack. Sumatriptan is given and subjects subsequently undergo MRI scans prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI).
干预措施: Cilostazol (Drug)
Effect of sumatriptan
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan and then undergo pharmacological induction of a migraine attack. Sumatriptan is given and subjects subsequently undergo MRI scans prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI).
干预措施: USPIO-MRI (Other)
Effect of sumatriptan
Subjects with habitual unilateral migraine without aura, undergo a baseline MRI scan and then undergo pharmacological induction of a migraine attack. Sumatriptan is given and subjects subsequently undergo MRI scans prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI).
干预措施: BBI-MRI (Other)
Pilot w/o cilostazol
Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan. Subjects are then MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI).
干预措施: Feraheme (Drug)
Pilot w/o cilostazol
Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan. Subjects are then MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI).
干预措施: USPIO-MRI (Other)
Pilot w/o cilostazol
Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan. Subjects are then MRI scanned prior to (BBI-MRI) and after Feraheme infusion (USPIO-MRI).
干预措施: BBI-MRI (Other)
Pilot w/ cilostazol
Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan and then receive cilostazol. Subjects are then MRI scanned prior (BBI-MRI) to and after Feraheme infusion (USPIO-MRI).
干预措施: Feraheme (Drug)
Pilot w/ cilostazol
Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan and then receive cilostazol. Subjects are then MRI scanned prior (BBI-MRI) to and after Feraheme infusion (USPIO-MRI).
干预措施: Cilostazol (Drug)
Pilot w/ cilostazol
Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan and then receive cilostazol. Subjects are then MRI scanned prior (BBI-MRI) to and after Feraheme infusion (USPIO-MRI).
干预措施: USPIO-MRI (Other)
Pilot w/ cilostazol
Subjects without habitual unilateral migraine without aura undergo a baseline MRI scan and then receive cilostazol. Subjects are then MRI scanned prior (BBI-MRI) to and after Feraheme infusion (USPIO-MRI).
干预措施: BBI-MRI (Other)
结局指标
主要结局
Change in USPIO uptake during attacks of unilateral migraine without aura compared to baseline
时间窗: 34 hours
On the first study day, migraine is induced with cilostazol, and intravenous infusion of Feraheme (USPIO) is delivered. On the second study day, USPIO-MRI is performed.
Change in arterial wall thickness during attacks of unilateral migraine without aura compared to baseline
时间窗: 6 hours
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed.
Change in arterial wall thickness during attacks of unilateral migraine without aura before and after sumatriptan
时间窗: 7 hours
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol ingestion, BBI-MRI is performed. Subjects are treated with sumatriptan, and BBI-MRI is repeated.
Change in arterial circumference as a proxy measure for vascular inflammation during attacks of unilateral migraine without aura compared to baseline
时间窗: 34 hours
On the first study day, migraine is induced with cilostazol, and at 4 hours and 28 hours after cilostazol ingestion, MR angiography is performed.
Change in arterial circumference as a proxy measure for vascular inflammation during unilateral attacks of migraine without aura before and after sumatriptan
时间窗: 36 hours
On the first study day, migraine is induced with cilostazol, and 4 hours after cilostazol, MR angiography is performed. Subjects are treated with sumatriptan, and MR angiography is repeated. 28 hours after cilostazol ingestion, MR angiography is performed again.
Change in USPIO uptake during attacks of unilateral migraine without aura before and after sumatriptan
时间窗: 36 hours
On the first study day, migraine is induced with cilostazol and subsequently treated with sumatriptan. Intravenous infusion of Feraheme (USPIO) is delivered, and on the second study day, USPIO-MRI is performed.
次要结局
未报告次要终点
研究者
Sabrina Khan
Medical Doctor and PhD student
Danish Headache Center