Hypersensitivity to Amylin in Post-Traumatic Headache

NCT07340775 | Not Yet Recruiting DMC

• 1 other identifier: H-21067689
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Brain Diseases; Headache Disorders; Nervous System Diseases; Pain; Central Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Post-Traumatic Headache; Peptide Hormones; Hormones; Peptides; Amino Acids, Peptides, and Proteins; Amylin; Pramlintide; Headache Disorders, Secondary; Hormones, Hormone Substitutes, and Hormone Antagonists

Keywords

Post-traumatic headache; Pain; Amylin

Outcome Measures

Primary Outcomes (1)

• Incidence of migraine-like headache

  Difference in incidence of migraine-like headache (0 to 12 hours) between pramlintide and placebo.

  12 hours

Secondary Outcomes (1)

• Headache Intensity Scores

  12 hours

Study Arms (2)

Amylin

EXPERIMENTAL

Pramlintide (Amylin) will be administered by intravenous infusion.

Drug: Amylin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Amylin DRUG

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

Amylin

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \> 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)
• 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

Sponsors & Collaborators

• Danish Headache Center: lead

Study Sites (1)

Rigshospitalet Glostrup

Glostrup Municipality, 2600, Denmark

Location

Related Publications (7)

• 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.

  PMID: 20194711 BACKGROUND

• 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.

  PMID: 26071095 BACKGROUND

• 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.

  PMID: 33772845 BACKGROUND

• 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.

  PMID: 31527806 BACKGROUND

• 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.

  PMID: 32102546 BACKGROUND

• 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.

  PMID: 1603351 BACKGROUND

• 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.

  PMID: 34022171 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

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

Interventions

Islet Amyloid Polypeptide

Intervention Hierarchy (Ancestors)

Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Amyloidogenic Proteins; Amyloid; Proteins

Central Study Contacts

Haidar Al-Khazali, MD, PhD

CONTACT

+4541598494; haidardk@hotmail.com

Hakan Ashina, MD, PhD

CONTACT

+4528102495; haakan.ashina@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD Fellow

Model Details: This single-center trial applies a randomized, double-blind, placebo-controlled, two-way crossover design.

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 14, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Anonymized data not published within this article will be made available on reasonable request from any qualified investigator.

Locations

DK (1)