MigraineNCT04260035
The Effects of a Long-lasting Infusion of Vasoactive Intestinal Peptide (VIP) in Episodic Migraine Patients
A study testing Vasoactive Intestinal Polypeptide (VIP) and Sterile saline in people with Migraine and Pain, run by Danish Headache Center at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Migraine, Pain, Neurologic Manifestations
- What is being tested?
- Vasoactive Intestinal Polypeptide (VIP) and Sterile saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteDenmark
- Study dates
- 19 May 2020to 15 Sep 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- Migraine, Pain, Neurologic Manifestations, Signs and Symptoms, Brain Diseases, Central Nervous System Diseases
- Being tested
- Vasoactive Intestinal Polypeptide (VIP), Sterile saline
- Medical subject headings
- Migraine Disorders, Pain, Neurologic Manifestations, Signs and Symptoms, Brain Diseases, Central Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vasoactive Intestinal Polypeptide (VIP)Drug
Also called Vasoactive Intestinal Peptide (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.
Sterile salineDrug
Also called Isotonic saline, 0.9% 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.
| Study group | Role | What they receive |
|---|---|---|
| Vasoactive Intestinal Polypeptide (VIP) | Active comparator | 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. Receives: Drug: Vasoactive Intestinal Polypeptide (VIP) |
| Sterile, isotonic, non-active saline (Placebo) | Placebo comparator | 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. Receives: Drug: Sterile saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of migraine-like attacks
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).
Measured: Before (-10 minutes) and after the drug administration (+12 hours)
Secondary outcomes (4)
Change in cranial hemodynamic
Change on diameter (mm) of superficial temporal artery (STA)
Measured: Before (-10 minutes) and after the drug administration (+3 hours)
Occurrence of headache and change of headache intensity scores
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.
Measured: Before (-10 minutes) and after the drug administration (+12 hours)
Change in Mean Arterial Pressure
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).
Measured: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
Change in Heart Rate
Heart rate was measured using an auto-inflatable cuff (Protocol, Oregon, USA).
Measured: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2020
- Study start19 May 2020
- Primary completion15 Sep 2020
- Study completion15 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Danish Headache Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lanfranco Pellesi, Danish Headache Center
- Investigators
- Messoud Ashina, MD, PhD, Study director, Danish Headache Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04260035
- Sponsor's protocol ID
- H-19075630
- Status last verified
- Oct 2020
- First submitted
- 5 Feb 2020
- Last updated
- 20 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 35432170Pellesi 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.
PubMed 34357396
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04260035
- Acronym / sponsor ID
- H-19075630
- Conditions
- Migraine, Pain, Neurologic Manifestations, Signs and Symptoms, Brain Diseases, Central Nervous System Diseases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Danish Headache CenterUniversity, hospital or other
- Study start
- 19 May 2020 (actual)
- Primary completion
- 15 Sep 2020 (actual)
- Study completion
- 15 Sep 2020 (actual)
- First posted
- 7 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vasoactive Intestinal Polypeptide (VIP) | Active comparator | Drug: 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. |
| Sterile, isotonic, non-active saline (Placebo) | Placebo comparator | Drug: Sterile salineIntravenous 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vasoactive Intestinal Polypeptide (VIP)Also: Vasoactive Intestinal Peptide (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. | Drug | Vasoactive Intestinal Polypeptide (VIP) |
| Sterile salineAlso: Isotonic saline, 0.9% saline20 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. | Drug | Sterile, isotonic, non-active saline (Placebo) |
Primary outcome
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).
4 secondary outcomes
Change in cranial hemodynamic
Time frame: Before (-10 minutes) and after the drug administration (+3 hours)
Occurrence of headache and change of headache intensity scores
Time frame: Before (-10 minutes) and after the drug administration (+12 hours)
Change in Mean Arterial Pressure
Time frame: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
Change in Heart Rate
Time frame: Before (-10 minutes) and after the drug administration (+3 hours and 20 minutes)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2020.
- Derived from this study: PubMed 35432170Pellesi 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.
- Derived from this study: PubMed 34357396Pellesi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Messoud Ashina, MD, PhD study director
Danish Headache Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vasoactive Intestinal Polypeptide (VIP) and Sterile saline in people with Migraine and Pain, run by Danish Headache Center at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of migraine-like attacks (time frame: Before (-10 minutes) and after the drug administration (+12 hours)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04260035, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2020.