Hypersensitivity to Amylin in Post-Traumatic Headache

NCT ID: NCT07340775

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

2028-12-31

Brief Summary

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Pramlintide is a peptide analogue of human amylin which is a vasoactive substance involved in the pathogenesis of headache. This study investigates whether pramlintide induces migraine-like headache in people with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI).

Detailed Description

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Amylin is a vasodilator released from nerve fibers within the trigeminovascular system, which is considered a key anatomical and physiological substrate in the pathogenesis of migraine and persistent post-traumatic headache (PTH). Persistent PTH attributed to mild traumatic brain injury frequently presents with migraine attacks, suggesting shared underlying mechanisms with migraine. This study aims to determine whether intravenous infusion of pramlintide, an analogue of amylin, can induce migraine-like headache in individuals with persistent post-traumatic headache. To test this hypothesis, we will conduct a randomized, double-blind, placebo-controlled, two-way crossover study.

Conditions

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Headache Disorders, Secondary Brain Diseases Headache Disorders Nervous System Diseases Central Nervous System Diseases Neurologic Manifestations Signs and Symptoms Pathological Conditions, Signs and Symptoms Post-Traumatic 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 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 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
* History of persistent headache attributed to mild traumatic injury to the head for ≥ 12 months and in accordance with the International Classification of Headache Disorders, 3rd Edition (ICHD-3)
* ≥ 4 monthly headache days on average across the 3 months prior to screening
* Provision of informed consent prior to initiation of any study-specific activities/procedures

Exclusion Criteria

* \> 1 mild traumatic injury to the head
* History of any primary or secondary headache disorder prior to mild traumatic injury to the head (except for infrequent episodic tension-type headache)
* History of moderate or severe injury to the head
* History of whiplash injury
* History of craniotomy
* History or evidence of any other clinically significant disorder, condition or disease (except for those outlined above) than, in the opinion of the site investigator, would pose a risk to subject safety or interfere with study evaluation, procedures or completion
* 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)
* Initiation, discontinuation, or change of dosing of prophylactic medications within 2 months prior to study inclusion
* Intake of acute medications (e.g. analgesics, triptans) within 48 hours of infusion start
* Baseline headache intensity of \>3 on an 11-point numeric rating scale (0 being no headache, 10 being the worst imaginable headache)
* Baseline migraine-like headache or self-reported baseline headache that mimics the subjects' usual migraine-like headache
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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Ksenija Cucanic

PhD Fellow

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)

Ashina H, Porreca F, Anderson T, Amin FM, Ashina M, Schytz HW, Dodick DW. Post-traumatic headache: epidemiology and pathophysiological insights. Nat Rev Neurol. 2019 Oct;15(10):607-617. doi: 10.1038/s41582-019-0243-8. Epub 2019 Sep 16.

Reference Type BACKGROUND
PMID: 31527806 (View on PubMed)

Ashina H, Iljazi A, Al-Khazali HM, Ashina S, Jensen RH, Amin FM, Ashina M, Schytz HW. Persistent post-traumatic headache attributed to mild traumatic brain injury: Deep phenotyping and treatment patterns. Cephalalgia. 2020 May;40(6):554-564. doi: 10.1177/0333102420909865. Epub 2020 Feb 26.

Reference Type BACKGROUND
PMID: 32102546 (View on PubMed)

Rasmussen BK, Olesen J. Symptomatic and nonsymptomatic headaches in a general population. Neurology. 1992 Jun;42(6):1225-31. doi: 10.1212/wnl.42.6.1225.

Reference Type BACKGROUND
PMID: 1603351 (View on PubMed)

Ashina H, Eigenbrodt AK, Seifert T, Sinclair AJ, Scher AI, Schytz HW, Lee MJ, De Icco R, Finkel AG, Ashina M. Post-traumatic headache attributed to traumatic brain injury: classification, clinical characteristics, and treatment. Lancet Neurol. 2021 Jun;20(6):460-469. doi: 10.1016/S1474-4422(21)00094-6.

Reference Type BACKGROUND
PMID: 34022171 (View on PubMed)

Related Links

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Other Identifiers

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H-21067689

Identifier Type: -

Identifier Source: org_study_id

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