The Effects of a Long-lasting Infusion of Vasoactive Intestinal Peptide (VIP) on Headache, Cranial Hemodynamic and Autonomic Symptoms in Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
Vasoactive intestinal peptide (VIP) is a peptide of 28 amino acid residues that belongs to the glucagon/secretin superfamily of peptides. It is produced in different regions of the nervous system, including the brain, trigeminovascular system and several autonomic nerves. Once released from neurons, it acts on vasoactive intestinal peptide receptor 1 (VPAC1), vasoactive intestinal peptide receptor 2 (VPAC2) and pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1), by mediating smooth muscle relaxation, vasodilation and water secretion. 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, sharing the activation of adenylate cyclase. 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 a long-lasting infusion of VIP may induce a prolonged vasodilation in the cerebral vessels and migraine, as a twenty-minute infusion of PACAP, is unknown.

Official Title
-----------------
The Effects of a Long-lasting Infusion of Vasoactive Intestinal Peptide (VIP) on Headache, Cranial Hemodynamic in Healthy Volunteers

Conditions
-----------------
Headache Disorders

Intervention / Treatment
-----------------
* Drug: Vasoactive Intestinal Peptide (VIP) and Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-60 years. 50-90 kg. Women of childbearing potential must use adequate contraception. Exclusion Criteria: Headache less than 48 hours before the tests start All primary headaches Daily consumption of drugs of any kind other than oral contraceptives Pregnant or nursing women. A cardiovascular disease of any kind, including cerebrovascular diseases.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VIP<br>To investigate the role of VIP on cranial hemodynamic and headache in healthy volunteers. | Drug: Vasoactive Intestinal Peptide (VIP) and Saline<br>* 12 healthy volunteers of both genders will be included in the main study. Participants will meet twice, with at least one week in between. The main study is a double-blind, randomized, cross-over trial among placebo (sterile saline, non-active substance) and VIP. Intravenous infusion of VIP / placebo (saline) will be conducted over 120 minutes. Patients will be asked after each trial day to record headache strength, accompanying symptoms, and drug use for up to 24 post-infusion.<br>|
| Placebo Comparator: Saline<br>To investigate the role of saline on cranial hemodynamic and headache in healthy volunteers. | Drug: Vasoactive Intestinal Peptide (VIP) and Saline<br>* 12 healthy volunteers of both genders will be included in the main study. Participants will meet twice, with at least one week in between. The main study is a double-blind, randomized, cross-over trial among placebo (sterile saline, non-active substance) and VIP. Intravenous infusion of VIP / placebo (saline) will be conducted over 120 minutes. Patients will be asked after each trial day to record headache strength, accompanying symptoms, and drug use for up to 24 post-infusion.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cranial hemodynamic | Change on diameter of superficial temporal artery. Change on diameter will be measured with milletimeter. | Before (-10 minutes) and after infusion (+2 hours) of VIP compared with before and after infusion of saline] | 
| Occurrence and change of headache | Occurrence of headache measured by numerical rating scale (NRS) | [Time Frame: Before (-10 minutes) and after infusion (+12 hours) of maxipost compared with before and after infusion of saline] |