- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04260035
The Effects of a Long-lasting Infusion of Vasoactive Intestinal Peptide (VIP) in Episodic Migraine Patients
The Effects of a Long-lasting Infusion of Vasoactive Intestinal Peptide (VIP) on Headache, Cranial Hemodynamic and Autonomic Symptoms in Episodic Migraine Patients Without Aura
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The vasoactive intestinal polypeptide (VIP) is a peptide of 28 amino acid residues that belongs to the glucagon/secretin superfamily of peptides. It is distributed in different regions of the nervous system, including several autonomic ganglia and the brain. Once released from neurons, it acts on the vasoactive intestinal peptide receptor 1 (VPAC1), the vasoactive intestinal peptide receptor 2 (VPAC2) and the pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1). All three belong to a family of G-protein coupled receptors, sharing the activation of adenylate cyclase and the increase in intracellular cyclic adenosine monophosphate (cAMP). The three receptors are involved in many physiological functions, among them the vasodilating and parasympathetic responses. VPAC1 and VPAC2 are expressed in dura mater vessels and are primarily responsible for the relaxation of arteries. PAC1 is located in the trigemino-autonomic system, but not in blood vessels. VIP shares the binding to the three aforementioned receptors with other peptides, including the pituitary adenylate cyclase-activating polypeptide-38 (PACAP38), and the pituitary adenylate cyclase-activating polypeptide-27 (PACAP27).
20-minute infusion of VIP and PACAPs in patients with migraine dilated cranial arteries. However, only PACAP27 and PACAP38 induced a sustained cranial vasodilation, and migraine like-attacks. VIP-induced cranial vasodilation was of short duration, and patients did not report migraine-like attacks. The discrepancy was ascribed to the preferential activation of the PAC1 receptor by PACAPs, but a monoclonal antibody against PAC1 receptor recently failed in migraine prevention. Currently, it is unknown whether the prolonged cranial vasodilation related with the appearance of migraine-like attacks. More recently, a two-hour infusion of VIP promoted a long-lasting cranial vasodilation and delayed headache in healthy volunteers, resembling the effect of PACAP27 and PACAP38, two closely related peptides causing migraine. Whether a long-lasting infusion of VIP may induce a sustained cranial vasodilation and migraine-like attacks in migraine patients, as a twenty-minute infusion of PACAP27 and PACAP38, is unknown.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Copenhagen
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Glostrup, Copenhagen, Denmark, 2600
- Danish Headache Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of migraine without aura as according to the International Classification
- Frequency of migraine attacks between one and six attacks within 8 weeks
- Weight: 50-90 kg
- Fertile women should use contraception. Fertile women do not include hysterectomies women or women who are postmenopausal for at least 2 years. Contraception includes either IUD, birth control pills, surgical sterilization of the woman or depot progesterone
Exclusion Criteria:
- Any other type of headache (including > 2 days of tension-type headache per month)
- Headache less than 48 hours before the start of the experiment
- Daily intake of any medicine other than oral contraception
- Pregnant or breastfeeding women
- Clinical signs of Hypertension (systolic blood pressure > 150 mmHg and / or diastolic blood pressure > 100 mmHg) and/or Hypotension (systolic blood pressure < 90 mm Hg and / or diastolic blood pressure < 50 mmHg)
- Cardiovascular disease of all kinds, including cerebrovascular disease
- Anamnestic or clinical signs of mental illness, abuse or smoking
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Vasoactive Intestinal Polypeptide (VIP)
Intravenous infusion of 8 pmol/Kg/min of Vasoactive Intestinal Polypeptide (VIP). The infusion is administered at constant speed by an automatic pump, lasting 120 minutes. |
20 episodic migraine patients without aura of both genders are randomized to receive a 2-hour infusion of VIP and/or sterile saline on two days, with at least one week in between.
Other Names:
|
Placebo Comparator: Sterile, isotonic, non-active saline (Placebo)
Intravenous infusion of sterile, isotonic, non-active saline 9 mg/ml (placebo).
The infusion is administered at constant speed by an automatic pump, lasting 120 minutes.
|
20 episodic migraine patients without aura of both genders are randomized to receive a 2-hour infusion of VIP and/or sterile saline on two days, with at least one week in between.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Occurrence of migraine-like attacks
Time Frame: Before (-10 minutes) and after the drug administration (+12 hours)
|
Migraine-like attack fulfilling either (i) or (ii): (i) Headache fulfilling criteria C and D for migraine without aura according to the International Classification od Headache Disorders: C. Headache has at least two of the following four characteristics: unilateral location; pulsating quality; moderate or severe pain intensity (moderate pain intensity is considered 5 or 4 on verbal rating scale); aggravation by cough (hospitalization phase) or causing avoidance of routine physical activity (out-hospital phase); D. During headache at least one of the following: nausea and/or vomiting; photophobia and phonophobia; (ii) Headache described as mimicking the patient's usual migraine attack and treated with acute migraine medication (rescue medication). |
Before (-10 minutes) and after the drug administration (+12 hours)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in cranial hemodynamic
Time Frame: Before (-10 minutes) and after the drug administration (+3 hours)
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Change on diameter (mm) of superficial temporal artery (STA)
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Before (-10 minutes) and after the drug administration (+3 hours)
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Occurrence of headache and change of headache intensity scores
Time Frame: Before (-10 minutes) and after the drug administration (+12 hours)
|
Headache intensity scores are measured by a numerical rating scale (NRS).
It is a verbally declared scale from 0 to 10, where 0 is no headache; 1 is a very mild headache, including a feeling of pressing or throbbing; 5 is a moderate headache; 10 is the worst imaginable headache.
|
Before (-10 minutes) and after the drug administration (+12 hours)
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Change in Mean Arterial Pressure
Time Frame: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
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Blood pressure was measured using an auto-inflatable cuff (Protocol, Oregon, USA).
Blood pressure was registered as mean arterial pressure (MAP), equal to diastolic blood pressure + 1/3 (systolic blood pressure - diastolic blood pressure).
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Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
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Change in Heart Rate
Time Frame: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
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Heart rate was measured using an auto-inflatable cuff (Protocol, Oregon, USA).
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Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Messoud Ashina, MD, PhD, Danish Headache Center
Publications and helpful links
General Publications
- Pellesi L, Al-Karagholi MA, De Icco R, Chaudhry BA, Lopez CL, Snellman J, Hannibal J, Amin FM, Ashina M. Plasma Levels of CGRP During a 2-h Infusion of VIP in Healthy Volunteers and Patients With Migraine: An Exploratory Study. Front Neurol. 2022 Apr 1;13:871176. doi: 10.3389/fneur.2022.871176. eCollection 2022.
- Pellesi L, Al-Karagholi MA, De Icco R, Coskun H, Elbahi FA, Lopez-Lopez C, Snellman J, Hannibal J, Amin FM, Ashina M. Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial. JAMA Netw Open. 2021 Aug 2;4(8):e2118543. doi: 10.1001/jamanetworkopen.2021.18543.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Headache Disorders, Primary
- Headache Disorders
- Nervous System Diseases
- Brain Diseases
- Migraine Disorders
- Neurologic Manifestations
- Central Nervous System Diseases
- Physiological Effects of Drugs
- Vasodilator Agents
- Gastrointestinal Agents
- Neuroprotective Agents
- Protective Agents
- Vasoactive Intestinal Peptide
Other Study ID Numbers
- H-19075630
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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