We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effects of a Long-lasting Infusion of Vasoactive Intestinal Peptide (VIP) in Episodic Migraine Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04260035
Recruitment Status : Completed
First Posted : February 7, 2020
Last Update Posted : October 20, 2020
Sponsor:
Information provided by (Responsible Party):
Lanfranco Pellesi, Danish Headache Center

Brief Summary:
Vasoactive intestinal peptide (VIP) is a peptide of 28 amino acid residues that belongs to the glucagon/secretin superfamily of peptides. Along with other neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP), it is released from the trigeminal afferents and exerts a strong vasodilating activity on the cranial vasculature. Especially, it shares 70% structure with PACAP and acts on the same receptors. But, unlike it, VIP cannot induce a long-lasting vasodilation and has a modest capability to induce migraine attacks. Whether it may induce migraine-like attacks in migraine patients, as a twenty-minute infusion of PACAP, is unknown.

Condition or disease Intervention/treatment Phase
Migraine Pain Neurologic Manifestations Signs and Symptoms Brain Diseases Central Nervous System Diseases Drug: Vasoactive Intestinal Polypeptide (VIP) Drug: Sterile saline Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: 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
Actual Study Start Date : May 19, 2020
Actual Primary Completion Date : September 15, 2020
Actual Study Completion Date : September 15, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Migraine
MedlinePlus related topics: Headache Migraine

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.

Drug: Vasoactive Intestinal Polypeptide (VIP)
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 Name: Vasoactive Intestinal Peptide (VIP)

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.
Drug: Sterile saline
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:
  • Isotonic saline
  • 0.9% saline




Primary Outcome Measures :
  1. 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).



Secondary Outcome Measures :
  1. Change in cranial hemodynamic [ Time Frame: Before (-10 minutes) and after the drug administration (+3 hours) ]
    Change on diameter (mm) of superficial temporal artery (STA)

  2. 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.

  3. Change in Mean Arterial Pressure [ Time Frame: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes) ]
    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).

  4. Change in Heart Rate [ Time Frame: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes) ]
    Heart rate was measured using an auto-inflatable cuff (Protocol, Oregon, USA).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04260035


Locations
Layout table for location information
Denmark
Danish Headache Center
Glostrup, Copenhagen, Denmark, 2600
Sponsors and Collaborators
Danish Headache Center
Investigators
Layout table for investigator information
Study Director: Messoud Ashina, MD, PhD Danish Headache Center
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Lanfranco Pellesi, Principal Investigator, Danish Headache Center
ClinicalTrials.gov Identifier: NCT04260035    
Other Study ID Numbers: H-19075630
First Posted: February 7, 2020    Key Record Dates
Last Update Posted: October 20, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Migraine Disorders
Nervous System Diseases
Brain Diseases
Central Nervous System Diseases
Neurologic Manifestations
Headache Disorders, Primary
Headache Disorders
Vasoactive Intestinal Peptide
Gastrointestinal Agents
Vasodilator Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs