NDPH Biomarker Study in Children and Adolescents

NCT ID: NCT06018025

Last Updated: 2025-12-01

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

COMPLETED

Total Enrollment

38 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-04-15

Study Completion Date

2025-05-29

Brief Summary

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This study will recruit pediatric patients with NDPH (New Daily Persistent Headache), characterize their headache in a standard manner, and treat the NDPH with standard medications used for treatment of headaches in this population. Response to treatment with CGRP blocking Ab medications will be evaluated. Biomarkers related to headache disorders will be measured before and after treatment.

Detailed Description

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Subjects age 10-18 with diagnosis of NDPH (International Classification of Headache Disorders D ICHD-3 criteria) will be recruited for the study. Consenting subjects will receive standard headache care and treatment, including treatment with CGRP Blocking Ab medications. Blood will be drawn before and after treatment, with assessment of Calcitonin Gene Related Peptid, Pituitary Adenylate Cyclase Activating Peptid (PACAP), Brain derived Neurotrophic factor (BDNF), Nerve Growth Factor (NGF), and Tumor Necrosis Factor alpha, and Vasointestinal peptic (VIP) before and after treatment.

Conditions

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New Persistent Daily Headache

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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NPDH (New Persistent Daily Headache)

Patients with new persistent daily headache (NDPH) ages 10-18 years will be recruited and consented by the study coordinator. Patients will be recruited from patients already established with the Duke Pediatric Neurology clinic with a diagnosis of NDPH, or after their initial visit to establish the diagnosis of NDPH through the Duke, pediatric neurology clinics, personal communication and networking, and through the Duke adult headache clinic.

CGRP antibody

Intervention Type DRUG

treatment with CGRP antibody for 4 months

Healthy (Normal) Controls

Children with normal development, aged 10-18 years, will be identified via the electronic health records of well-child visits in Duke Children's Hospital, community advertising and through networking with colleagues and friends.

Exclusion: 1) History of concussion or head injury 2) Psychiatric disorders 3) History of migraines or other headache disorder treated in the past 4) Known structural brain lesions (tumor, hydrocephalus, congenital anomalies)

No interventions assigned to this group

Chronic Migraine

Patients between 10-18 yrs of age:

A) Headache (migraine-like or tension-type-like) on ≥15 days/month for \>3 months, and fulfilling criteria B and C, B) Occurring in a patient who has had at least five attacks fulfilling criteria B-D for 1.1 Migraine without aura and/or criteria B and C for 1.2 Migraine with aura C) On ≥8 days/month for \>3 months, fulfilling any of the following (1) criteria C and D for 1.1 Migraine without aura 2) criteria B and C for 1.2 Migraine with aura 3) believed by the patient to be migraine at onset and relieved by a triptan or ergot derivative D) Not better accounted for by another ICHD-3 diagnosis

CGRP antibody

Intervention Type DRUG

treatment with CGRP antibody for 4 months

Interventions

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CGRP antibody

treatment with CGRP antibody for 4 months

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients between 10-18 yo with diagnosis of new daily persistent headache (ICHD-3 criteria) who have normal developmental history for age
* Subject and parent legal guardian able to communicate in English, understand and consent to study
* Subject will to undergo monthly injections at home for treatment of NDPH
* Normal neuro imaging
* No prior treatment with CGRP blocking medications or botulinum toxin

Exclusion Criteria

* History of Reynauds syndrome
* History of concussion or prior neurosurgery
* Any structural brain lesion including hydrocephalus, congenital anomalies (including chiari malformation)
* History of psychiatric disorders
* History of any headache disorder (including migraine) prior to the diagnosis of NDPH
* Pregnancy
* Prior treatment with any CGRP blocking medication
* Treatment with Botulinum toxin injections previously
* Any other condition that in the opinion of the PI would interfere with the planned study treatment
Minimum Eligible Age

10 Years

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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International Headache Society

UNKNOWN

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Klaus Werner, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Duke University Health System

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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Greene KA, Gentile CP, Szperka CL, Yonker M, Gelfand AA, Grimes B, Irwin SL. Calcitonin Gene-Related Peptide Monoclonal Antibody Use for the Preventive Treatment of Refractory Headache Disorders in Adolescents. Pediatr Neurol. 2021 Jan;114:62-67. doi: 10.1016/j.pediatrneurol.2020.09.014. Epub 2020 Oct 5.

Reference Type BACKGROUND
PMID: 33232919 (View on PubMed)

Demartini C, Francavilla M, Zanaboni AM, Facchetti S, De Icco R, Martinelli D, Allena M, Greco R, Tassorelli C. Biomarkers of Migraine: An Integrated Evaluation of Preclinical and Clinical Findings. Int J Mol Sci. 2023 Mar 10;24(6):5334. doi: 10.3390/ijms24065334.

Reference Type BACKGROUND
PMID: 36982428 (View on PubMed)

Gelfand AA, Robbins MS, Szperka CL. New Daily Persistent Headache-A Start With an Uncertain End. JAMA Neurol. 2022 Aug 1;79(8):733-734. doi: 10.1001/jamaneurol.2022.1727. No abstract available.

Reference Type BACKGROUND
PMID: 35788252 (View on PubMed)

Goadsby PJ. New daily persistent headache: a syndrome, not a discrete disorder. Headache. 2011 Apr;51(4):650-3. doi: 10.1111/j.1526-4610.2011.01872.x.

Reference Type BACKGROUND
PMID: 21457252 (View on PubMed)

Peng KP, Rozen TD. Update in the understanding of new daily persistent headache. Cephalalgia. 2023 Feb;43(2):3331024221146314. doi: 10.1177/03331024221146314.

Reference Type BACKGROUND
PMID: 36759317 (View on PubMed)

Gladstein J, Holden EW. Chronic daily headache in children and adolescents: a 2-year prospective study. Headache. 1996 Jun;36(6):349-51. doi: 10.1046/j.1526-4610.1996.3606349.x.

Reference Type BACKGROUND
PMID: 8707551 (View on PubMed)

Hanci F, Kilinc YB, Kilinc E, Turay S, Dilek M, Kabakus N. Plasma levels of vasoactive neuropeptides in pediatric patients with migraine during attack and attack-free periods. Cephalalgia. 2021 Feb;41(2):166-175. doi: 10.1177/0333102420957588. Epub 2020 Sep 9.

Reference Type BACKGROUND
PMID: 32903061 (View on PubMed)

Evers S. CGRP in Childhood and Adolescence Migraine: (Patho)physiological and Clinical Aspects. Curr Pain Headache Rep. 2022 Jun;26(6):475-480. doi: 10.1007/s11916-022-01047-5. Epub 2022 Mar 30.

Reference Type BACKGROUND
PMID: 35353359 (View on PubMed)

Christensen CE, Ashina M, Amin FM. Calcitonin Gene-Related Peptide (CGRP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Migraine Pathogenesis. Pharmaceuticals (Basel). 2022 Sep 27;15(10):1189. doi: 10.3390/ph15101189.

Reference Type BACKGROUND
PMID: 36297301 (View on PubMed)

Vollesen ALH, Amin FM, Ashina M. Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine. Neurotherapeutics. 2018 Apr;15(2):371-376. doi: 10.1007/s13311-017-0596-x.

Reference Type BACKGROUND
PMID: 29464574 (View on PubMed)

Sarchielli P, Caproni S, Costa C, Szok D, Tajti J. Chapter 10: Biochemistry of Primary Headaches. Pathophysiology of Headaches 2015: 185-216.

Reference Type BACKGROUND

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)

Moyes C, Belaghi R, Webster RJ, Whitley N, Pohl D. Cognitive Behavioral Therapy for Children With Headaches: Will an App Do the Trick? J Child Neurol. 2023 Mar;38(3-4):169-177. doi: 10.1177/08830738231170067. Epub 2023 Apr 25.

Reference Type BACKGROUND
PMID: 37097885 (View on PubMed)

McAbee GN, Morse AM, Assadi M. Pediatric Aspects of Headache Classification in the International Classification of Headache Disorders-3 (ICHD-3 beta version). Curr Pain Headache Rep. 2016 Jan;20(1):7. doi: 10.1007/s11916-015-0537-5.

Reference Type BACKGROUND
PMID: 26749046 (View on PubMed)

Begasse de Dhaem O, Rizzoli P. Refractory Headaches. Semin Neurol. 2022 Aug;42(4):512-522. doi: 10.1055/s-0042-1757925. Epub 2022 Nov 2.

Reference Type BACKGROUND
PMID: 36323303 (View on PubMed)

Nierenburg H, Newman LC. Update on New Daily Persistent Headache. Curr Treat Options Neurol. 2016 Jun;18(6):25. doi: 10.1007/s11940-016-0408-3.

Reference Type BACKGROUND
PMID: 27080086 (View on PubMed)

Mack KJ. What incites new daily persistent headache in children? Pediatr Neurol. 2004 Aug;31(2):122-5. doi: 10.1016/j.pediatrneurol.2004.02.006.

Reference Type BACKGROUND
PMID: 15301832 (View on PubMed)

Li D, Rozen TD. The clinical characteristics of new daily persistent headache. Cephalalgia. 2002 Feb;22(1):66-9. doi: 10.1046/j.1468-2982.2002.00326.x.

Reference Type BACKGROUND
PMID: 11993616 (View on PubMed)

Baron EP, Rothner AD. New daily persistent headache in children and adolescents. Curr Neurol Neurosci Rep. 2010 Mar;10(2):127-32. doi: 10.1007/s11910-010-0097-3.

Reference Type BACKGROUND
PMID: 20425237 (View on PubMed)

Mozafarihashjin M, Togha M, Ghorbani Z, Farbod A, Rafiee P, Martami F. Assessment of peripheral biomarkers potentially involved in episodic and chronic migraine: a case-control study with a focus on NGF, BDNF, VEGF, and PGE2. J Headache Pain. 2022 Jan 6;23(1):3. doi: 10.1186/s10194-021-01377-6.

Reference Type BACKGROUND
PMID: 34991456 (View on PubMed)

Other Identifiers

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Pro00113907

Identifier Type: -

Identifier Source: org_study_id

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