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Trial record 36 of 231 for:    CALCITONIN SALMON

Clinical Characteristics and Pathophysiology of Post-Traumatic Headache

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ClinicalTrials.gov Identifier: NCT03791515
Recruitment Status : Recruiting
First Posted : January 1, 2019
Last Update Posted : January 1, 2019
Sponsor:
Information provided by (Responsible Party):
Henrik Schytz, Danish Headache Center

Brief Summary:
To better understand the clinical characteristics and complex pathophysiological events that constitute persistent post-traumatic headache (PPTH) and to identify possible calcitonin gene-related peptide (CGRP) hypersensitivity in PPTH patients.

Condition or disease Intervention/treatment Phase
Post-Traumatic Headache Concussion, Mild Drug: Calcitonin Gene-Related Peptide Drug: Placebo Not Applicable

Detailed Description:
The present project will embark upon identifying novel PTH-specific biomarkers by incorporating a plethora of scientific approaches. First, clinical biomarkers will be assessed by deep phenotyping of clinical characteristics and associated comorbidities using a semi-structured interview and multiple validated questionnaires. Second, biochemical biomarkers will be determined by plasma levels measurements of blood markers for headache hypersensitivity and neuronal/axonal damage. Third, imaging biomarkers will be established by magnetic resonance imaging (MRI) to assess structural and functional changes in the brain. Lastly, molecular biomarkers will be identified by examining whether intravenous infusion of calcitonin gene-related peptide (CGRP) provokes headache attacks mimicking the usual headache phenotype in subjects with PTH. This would determine whether PTH patients exhibit hypersensitivity to CGRP (molecular biomarker) and advance our understanding of the complex pathophysiological events that constitute the headache phenotypes in PTH sufferers.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

100 patients with PPTH and 100 healthy controls will undergo a deep phenotyping of clinical characteristics and associated comorbidities. This is followed by a single MRI-session for all subjects.

Lastly, the 30 patients with PPTH will participate in a randomized, double-blind, placebo-controlled, 2-way crossover study. These patients will be allocated to receive intravenous infusion of CGRP or placebo (isotonic saline) over 20 minutes on 2 study days.

Masking: None (Open Label)
Primary Purpose: Other
Official Title: Clinical Characteristics and Pathophysiology of Post-Traumatic Headache
Actual Study Start Date : July 26, 2018
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Calcitonin Gene-Related Peptide (CGRP)

30 patients with PPTH will be allocated to receive intravenous infusion of 1.5 µg/min calcitonin-gene related peptide over 20 minutes

Other Name: CGRP

Drug: Calcitonin Gene-Related Peptide

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 1.5 µg/min CGRP over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Other Name: CGRP

Placebo Comparator: Placebo

30 patients with PPTH wil be allocated to receive 40 mL Placebo (isotonic saline) over 20 minutes.

Other Name: Isotonic Saline

Drug: Placebo

A randomized clinical trial with a double-blinded, randomized, placebo-controlled crossover design. 30 PPTH patients will be included. All participants will receive continuous intravenous infusion of 40 mL placebo (isotonic saline) over 20 min.

The following variables will be recorded before, during and after infusion (every 10 min over 60 min): headache intensity on a verbal rating scale from 0 to 10 and headache characteristics. At 90 min, participants will be discharged and instructed to fill out a headache diary for 24 hours from start of infusion.

Other Name: Isotonic Saline




Primary Outcome Measures :
  1. Headache Characteristics [ Time Frame: 50 minutes ]
    Headache characteristics will be assessed using a semi-structured interview.

  2. Headache Characteristics [ Time Frame: 10 minutes ]
    Headache characteristics will be assessed using Headache Under-Response to Treatment Index (HURT-Index) questionnaire. The total score ranges from 0 to 24 with a higher score indicating a lower effectiveness of intervention against headache.

  3. Cognitive Function [ Time Frame: 10 minutes ]
    Cognitive function will be assessed using Montreal Cognitive Assessment (MoCA) questionnaire. The total score ranges from 0 to 30 points. The MoCA is divided into 7 subscores: visuospatial/executive (5 points); naming (3 points); memory (5 points for delayed recall); attention (6 points); language (3 points); abstraction (2 points); and orientation (6 points). One point is added if the subject has ≤12 years of education. A total of 30 points may be given. A score ≤25 indicates some degree of cognitive impairment.

  4. Depression [ Time Frame: 10 minutes ]

    Depression will be assessed using Hospital Anxiety and Depression Scale (HADS) questionnaire. The total score ranges from 0-21.

    A score of 0-7 points is regarded as being in the normal range. A score of 8-10 points is suggestive of a depressive state (borderline abnormal).

    A score of 11-21 points indicates a probable presence of a depressive state (abnormal).


  5. Anxiety [ Time Frame: 10 minutes ]

    Anxiety will be assessed using Hospital Anxiety and Depression Scale (HADS) questionnaire.

    The total score ranges from 0-21. A score of 0-7 points is regarded as being in the normal range. A score of 8-10 points is suggestive of a state of anxiety (borderline abnormal).

    A score of 11-21 points indicates a probable presence of an anxiety disorder (abnormal).


  6. Allodynia [ Time Frame: 10 minutes ]

    Allodynia will be assessed using Allodynia Symptom Checklist (ASC-12) questionnaire. The total score ranges from 0-24 points.

    A score of 0-2 suggests no allodynia. A score of 3-5 suggests mild allodynia. A score of 6-8 suggests moderate allodynia. A score of 9 or more suggests severe allodynia.


  7. Post-Traumatic Stress Disorder [ Time Frame: 10 minutes ]
    Post-traumatic stress disorder will be assessed using Harvard Trauma Questionnaire (HTQ). The total score ranges from 16-64. The total score is divided with 16 and a clinical cut-off score of 2.5 is set to be indicative of PTSD.

  8. Quality of Sleep: Pittsburgh Sleep Quality Index (PSQ-I) [ Time Frame: 10 minutes ]
    Quality of Sleep will be assessed using Pittsburgh Sleep Quality Index (PSQ-I). The measure consists of 19 individual items, creating 7 components that produce one global score. The total PSQ-I score ranges from 0 to 21 with lower scores indicating a healthier sleep quality.

  9. Muscle Tenderness [ Time Frame: 10 minutes ]
    Muscle tenderness will be assessed using Total Tenderness Score (TTS). The total score ranges from 0-48 with higher scores indicating a higher degree of muscle tenderness.

  10. Pressure Pain Threshold [ Time Frame: 10 minutes ]
    Pressure Pain Threshold will be assessed using an Algometer.

  11. Cortical Density [ Time Frame: 10 minutes ]
    Cortical density will be assessed using Voxel-Based Morphometry.

  12. Cortical Thickness [ Time Frame: 10 minutes ]
    Cortical thickness will be assessed using Surface-Based Morphometry

  13. Number and Location of Microhemorrhages [ Time Frame: 6 minutes ]
    The number and location of microhemorrhages will be assessed using Susceptibility-Weighted Imaging.

  14. White Matter Structural Fiber Integrity [ Time Frame: 10 minutes ]
    The white matter structural fiber integrity will be assessed using Diffusion Tensor Imaging

  15. Number and Location of White Matter Lesions [ Time Frame: 6 minutes ]
    The number and location of white matter lesions will be assessed using T2-weighted Fluid-Attenuated Inversion Recovery.

  16. Cerebral Blood Flow [ Time Frame: 7 minutes ]
    Cerebral blood flow will be assessed using arterial spin labelling (ASL).

  17. Brain Network Functional Connectivity [ Time Frame: 11 minutes ]
    Brain network functional connectivity will be assessed using blood oxygen level-dependent functional magnetic resonance imaging.

  18. Incidence of Headache Exacerbation with Migraine-Like Features [ Time Frame: 60 minutes ]

    Migraine-like features are defined as headache fulfilling at least two of the following four characteristics:

    1. Unilateral location
    2. Pulsating quality
    3. Moderate or severe pain intensity
    4. Aggravation by or causing avoidance of routine physical activity (e.g. walking or climbing stairs)

    And during headache at least one of the following must be fulfilled:

    1. Nausea and/or vomiting
    2. Photophobia and phonophobia
    3. Headache mimicking the usual exacerbated headache with migraine-like features

    If the participant fulfills these criteria at baseline, then incidence of exacerbated headache with migraine-like features is defined as:

    - An increase in headache intensity combined with an increase in the degree nausea and/or photophobia and phonophobia (based on a mild / moderate / severe scale)


  19. Headache Area under the Curve [ Time Frame: 12 hours ]
    Headache area under the curve is defined as headache intensity x duration up to 12 h after CGRP infusion

  20. Time to Maximum Headache [ Time Frame: 12 hours ]
    Time to maximum headache score on CGRP day compared to placebo day will be assessed using a headache questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria for PPTH patients:

  • 18-65 years of age
  • Subject has PPTH in accordance with the diagnostic criteria of the International Headache Society (IHS)
  • Concussion (mild traumatic brain injury) occured > 12 months ago
  • Subject, who are fertile women, must be on safe contraceptives

Exclusion Criteria for PPTH patients:

  • Pre-trauma existing primary headache disorder (maximum 1 day/per month with tension-type headache) and medication-overuse headache
  • > 1 episode with a sustained concussion
  • Whiplash
  • Pregnant or lactating women
  • Cardiovascular disease of any kind
  • Hypertension on the experimental day
  • Hypotension on the experimental day
  • Pre-trauma existing psychiatric disorder of any kind - unless well-regulated
  • Any anamnestic or clinical signs of any kind deemed relevant for the study by the physician examining the subject
  • Any MRI contraindication and a wish of not being informed about unexpected MRI changes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03791515


Contacts
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Contact: Henrik Schytz, MD 004528761824 henrik.winther.schytz.01@regionh.dk

Locations
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Denmark
Danish Headache Center Recruiting
Glostrup, Denmark, 2600
Contact: Henrik Schytz, MD         
Sponsors and Collaborators
Danish Headache Center
Investigators
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Principal Investigator: Henrik Schytz, MD Associate Professor

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Responsible Party: Henrik Schytz, Associate Professor of Neurology, Danish Headache Center
ClinicalTrials.gov Identifier: NCT03791515     History of Changes
Other Study ID Numbers: H-18011477
First Posted: January 1, 2019    Key Record Dates
Last Update Posted: January 1, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Calcitonin
Salmon calcitonin
Calcitonin Gene-Related Peptide
Katacalcin
Post-Traumatic Headache
Brain Concussion
Headache
Pain
Neurologic Manifestations
Signs and Symptoms
Headache Disorders, Secondary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Injuries, Traumatic
Brain Injuries
Craniocerebral Trauma
Trauma, Nervous System
Head Injuries, Closed
Wounds and Injuries
Wounds, Nonpenetrating
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Bone Density Conservation Agents
Vasodilator Agents