Amylin-Induced Migraine Attacks Without Aura

NCT ID: NCT07340788

Last Updated: 2026-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-28

Study Completion Date

2028-10-30

Brief Summary

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Pramlintide is a peptide analogue of human amylin which is a vasoactive signaling molecule involved in the pathogenesis of migraine. This study investigates whether pramlintide induces migraine attacks without aura in people with migraine without aura.

Detailed Description

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Amylin is a vasoactive substance that acts on vascular smooth muscle and can cause vasodilation. It is naturally present in the trigeminovascular system, an important structure involved in headache development. Recent studies indicate that intravenous infusion of pramlintide, an amylin analogue, can trigger migraine attacks in people with migraine. This study aims to determine whether intravenous pramlintide can induce migraine attacks without aura in individuals who experience migraine without aura. To test this, the investigators will conduct a randomized, double-blind, placebo-controlled, two-way crossover trial.

Conditions

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Headache Disorders, Primary Headache Disorders Brain Diseases Nervous System Diseases Central Nervous System Diseases Neurologic Manifestations Signs and Symptoms Pathological Conditions, Signs and Symptoms Migraine Disorders Headache Pain Peptide Hormones Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Peptides Amino Acids, Peptides, and Proteins Amylin Pramlintide

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Amylin

Pramlintide (Amylin) will be administered by intravenous infusion.

Group Type EXPERIMENTAL

Amylin

Intervention Type DRUG

The participants will receive continuous intravenous infusion of 20 mL (6 μg/min) of pramlintide (amylin) over 20 minutes.

Placebo

Placebo (isotonic saline) will be administered by intravenous infusion.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

The participants will receive continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.

Interventions

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Amylin

The participants will receive continuous intravenous infusion of 20 mL (6 μg/min) of pramlintide (amylin) over 20 minutes.

Intervention Type DRUG

Placebo

The participants will receive continuous intravenous infusion of 20 mL of placebo (isotonic saline) over 20 minutes.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age 18 to 65 years of age upon entry into screening
* A body weight of 50 to 100 kg
* History of migraine without aura for ≥12 months and in accordance with ICHD-3
* Between 1-5 monthly migraine days without aura on average across the 3 months prior to screening
* Provision of informed consent prior to initiation of any study-specific activities/procedures

Exclusion Criteria

* Any history of a primary or secondary headache disorder other than migraine without aura and infrequent episodic tension-type headache
* Any history of moderate to severe traumatic brain injury
* Any history of cardiovascular disease, including cerebrovascular diseases
* Any history of pulmonary disease
* Any other clinically significant disorders, conditions, or diseases that might impact the safety of the subject or interfere with the study's evaluation, procedures, or completion, aside from those mentioned above. This includes any relevant medical history or evidence that, in the opinion of the site investigator, might pose a risk to the subject or impact the validity of the study results
* The subject is at risk of self-harm or harm to others as evidenced by past suicidal behavior
* Female subjects of childbearing potential with a positive pregnancy test during any study visit
* Cardiovascular disease of any kind, including cerebrovascular diseases
* Hypertension (systolic blood pressure of ≥150 mmHg and/or diastolic blood pressure of ≥100 mmHg) prior to the start of infusion on the experimental day
* Hypotension (systolic blood pressure of ≤90 mmHg and/or diastolic blood pressure of ≤50 mmHg)
* Abnormalities on the electrocardiogram that, in the opinion of the site investigator, might pose a risk to the subject or impact the validity of the study results
* Daily use of any medication other than contraceptives
* Intake of any medication other than contraceptives within 48 hours of infusion start
* Intake of caffeine, nicotine, and alcohol within 12 hours of infusion start
* Headache of any intensity within 48 hours of infusion start
* Migraine attack within 48 hours of infusion start
* Aura within 48 hours of infusion start
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Danish Headache Center

OTHER

Sponsor Role lead

Responsible Party

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Håkan Ashina

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Rigshospitalet Glostrup

Glostrup Municipality, , Denmark

Site Status

Countries

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Denmark

Central Contacts

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Haidar Al-Khazali, MD, PhD

Role: CONTACT

+4541598494

Hakan Ashina, MD, PhD

Role: CONTACT

+4528102495

Facility Contacts

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Haidar Al-Khazali, MD, PhD

Role: primary

+4541598494

Hakan Ashina, MD, PhD

Role: backup

+4528102495

References

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Asmar M, Bache M, Knop FK, Madsbad S, Holst JJ. Do the actions of glucagon-like peptide-1 on gastric emptying, appetite, and food intake involve release of amylin in humans? J Clin Endocrinol Metab. 2010 May;95(5):2367-75. doi: 10.1210/jc.2009-2133. Epub 2010 Mar 1.

Reference Type BACKGROUND
PMID: 20194711 (View on PubMed)

Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. Amylin: Pharmacology, Physiology, and Clinical Potential. Pharmacol Rev. 2015 Jul;67(3):564-600. doi: 10.1124/pr.115.010629.

Reference Type BACKGROUND
PMID: 26071095 (View on PubMed)

Ghanizada H, Al-Karagholi MA, Walker CS, Arngrim N, Rees T, Petersen J, Siow A, Morch-Rasmussen M, Tan S, O'Carroll SJ, Harris P, Skovgaard LT, Jorgensen NR, Brimble M, Waite JS, Rea BJ, Sowers LP, Russo AF, Hay DL, Ashina M. Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients. Ann Neurol. 2021 Jun;89(6):1157-1171. doi: 10.1002/ana.26072. Epub 2021 Apr 8.

Reference Type BACKGROUND
PMID: 33772845 (View on PubMed)

Hansen JM, Hauge AW, Olesen J, Ashina M. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia. 2010 Oct;30(10):1179-86. doi: 10.1177/0333102410368444. Epub 2010 May 12.

Reference Type BACKGROUND
PMID: 20855363 (View on PubMed)

Ashina M, Hansen JM, Do TP, Melo-Carrillo A, Burstein R, Moskowitz MA. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019 Aug;18(8):795-804. doi: 10.1016/S1474-4422(19)30185-1. Epub 2019 May 31.

Reference Type BACKGROUND
PMID: 31160203 (View on PubMed)

Ashina M, Terwindt GM, Al-Karagholi MA, de Boer I, Lee MJ, Hay DL, Schulte LH, Hadjikhani N, Sinclair AJ, Ashina H, Schwedt TJ, Goadsby PJ. Migraine: disease characterisation, biomarkers, and precision medicine. Lancet. 2021 Apr 17;397(10283):1496-1504. doi: 10.1016/S0140-6736(20)32162-0. Epub 2021 Mar 25.

Reference Type BACKGROUND
PMID: 33773610 (View on PubMed)

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

Reference Type BACKGROUND
PMID: 29368949 (View on PubMed)

Ashina M. Migraine. N Engl J Med. 2020 Nov 5;383(19):1866-1876. doi: 10.1056/NEJMra1915327. No abstract available.

Reference Type BACKGROUND
PMID: 33211930 (View on PubMed)

Related Links

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Other Identifiers

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H-24025082

Identifier Type: -

Identifier Source: org_study_id

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