Amylin and CGRP Head to Head Provocation in Migraine Without Aura Patients

Amylin and CGRP Migraine Provocation in Migraine Without Aura Patients

Amylin and calcitonin gene related peptide (CGRP) are related to the same peptide family. Both share 16 out of 37 amino acids and can activate each others receptor. CGRP is implicated in migraine pathophysiology but the role of Amylin and its receptor in migraine is not fully clarified.

Study Overview

• Status: Completed
• Conditions: Migraine Without Aura
• Intervention / Treatment: Other: Amylin (Pramlintide); Other: CGRP

Detailed Description

Amylin is a peptide hormone that binds to a G-protein coupled receptor (GPCR). amylin was originally found in the pancreas (Beta Cell of Islets of Langerhans) but also shown to be present in the trigeminal ganglion, hind horn ganglia and perivascular nerve fibers.

Amylin has many similarities with CGRP. Amylin and CGRP share 16 out 37 amino acids. Both peptides can activate the amylin 1 subtype (AMY1)receptor with high affinity and reported to have more similar physiological and pharmacological effects.

In addition, both peptides increase the intracellular concentration of cyclic AMP (cAMP) which has a central role in migraine pathophysiology.

The aim of the study is pin point the role of amylin and amylin receptor compare to CGRP in migraine pathophysiology.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Danish Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Migraine patients meeting International Headache Society (IHS) criteria for migraine without aura of both sexes, 18-60 year, 50-100 kg.
• Fertile women should use safe contraception. Fertile women do not include hysterectomized women or women who are postmenopausal for at least 2 years. Safe contraception includes either Intra Uterine Device (IUD), birth control pills, surgical sterilization of the woman or depot progestogen.

Exclusion Criteria:

• Tension Type headache for more than 5 days the month on average in the last year.
• All other primary headaches .
• Headache later than 48 hours before trial start.
• Daily intake of any medicine other than oral contraception.
• Ingestion of any form of medicinal product later than 4 times the plasma half-life substance (on trial day), except for oral contraception.
• Pregnant or breastfeeding women.
• Headache on the test day or later than 48 hours prior to administration of trial medicine / placebo
• Migraine within 5 days before the trial date.
• Ancestral information or clinical signs of (on the day of inclusion):
• Hypertension (systolic blood pressure> 150 mmHg and / or diastolic blood pressure> 100 mmHg)
• 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 or abuse.
• Patients with glaucoma or prostatic hyperplasia
• Anamnestic or clinical signs of diseases of any kind such as the investigating physician is considered relevant for participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Amylin (Pramlintide); Pramlintide intravenous infusion 120 micrograms over 20 minutes	Other: Amylin (Pramlintide); Pramlintide is a amylin analog. It will be given intravenously at the rate of 120 micrograms over 20 minutes .
Other: CGRP; CGRP intravenous infusion 30 micrograms over 20 minutes	Other: CGRP; CGRP It will be given intravenously at the rate of 30 microgram over 20 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Migraine incidence	Before (-10 min) and after infusion (+12 hours) of amlyin compared with before and after infusion of CGRP based on questionnaire reported headache and associated symptoms	12 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dilatation of Arteria radialis and arteria temporalis superficialis	Dermascan will be used to measure the above mentioned Radial and temporal arteries diameter.	2 hours
Facial flushing	Flushing will measured by laser contrast imaging	2 hours
Plasma blood samples	Measumrent of amylin and CGRP peptides in the plasma in picomol/L	2 hours
Headache intensity	Measured by visual analog score (VAS) ( 0 to 10). Change in area under curve (AUC)	12 hours

Collaborators and Investigators

• Sponsor: Danish Headache Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2018
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: June 28, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 25, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine without Aura; Hypoglycemic Agents; Physiological Effects of Drugs; Pramlintide
• Other Study ID Numbers: H-17035931

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No