NDPH Biomarker Study in Children and Adolescents

NCT06018025 | Completed

• 1 other identifier: Pro00113907
• Study Type: observational
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

New Persistent Daily Headache

Keywords

NPDH; CGRP; PACAP; BDNF; NGF; TNF-alpha; VIP; biomarker

Outcome Measures

Primary Outcomes (6)

• Change in Calcitonin Gene Related Peptide (CGRP) levels in blood

  biomarker

  baseline and 4 months

• Change in Pituitary Adenylate Cyclase-activating Peptide (PACAP) levels in blood

  protein biomarker

  baseline and 4 months

• Change in Brain derived Neurotrophic factor (BDNF) levels in blood

  protein biomarker

  baseline and 4 months

• Change in Nerve Growth Factor (NGF) levels in blood

  protein biomarker

  baseline and 4 months

• Change in Tumor Necrosis Factor alpha levels in blood

  protein biomarker

  baseline and 4 months

• Change in Vaso Intestinal peptide(VIP) levels in blood

  protein biomarker

  baseline and 4 months

Secondary Outcomes (5)

• Disability Scoring

  0 to 4 months

• Change in Headache frequency

  0 to 4 months

• Screen for Child Anxiety Related Disorders (SCARED)

  at enrollment

• Patient Health Questionnaire-9 modified for Adolescents administered after recruitment

  at enrollment

• Change in Headache Pain Intensity

  0 to 4 months

Study Arms (3)

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.

Drug: CGRP antibody

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)

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

Drug: CGRP antibody

Interventions

CGRP antibody DRUG

treatment with CGRP antibody for 4 months

Chronic Migraine; NPDH (New Persistent Daily Headache)

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

10 patients with NPDH age 10-18yrs 10 patients with chronic migraine age 10-18 yrs 10 normal controls age 10-18 yrs

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• International Headache Society: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (20)

• 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.

  PMID: 33232919 BACKGROUND

• 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.

  PMID: 36982428 BACKGROUND

• 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.

  PMID: 35788252 BACKGROUND

• 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.

  PMID: 21457252 BACKGROUND

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

  PMID: 36759317 BACKGROUND

• 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.

  PMID: 8707551 BACKGROUND

• 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.

  PMID: 32903061 BACKGROUND

• 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.

  PMID: 35353359 BACKGROUND

• 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.

  PMID: 36297301 BACKGROUND

• 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.

  PMID: 29464574 BACKGROUND

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

  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.

  PMID: 33773610 BACKGROUND

• 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.

  PMID: 37097885 BACKGROUND

• 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.

  PMID: 26749046 BACKGROUND

• 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.

  PMID: 36323303 BACKGROUND

• 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.

  PMID: 27080086 BACKGROUND

• 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.

  PMID: 15301832 BACKGROUND

• 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.

  PMID: 11993616 BACKGROUND

• 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.

  PMID: 20425237 BACKGROUND

• 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.

  PMID: 34991456 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

whole blood, serum,

Study Officials

• Klaus Werner, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 4 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2023
• First Posted: August 30, 2023
• Study Start: April 15, 2024
• Primary Completion: May 29, 2025
• Study Completion: May 29, 2025
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)