NDPH Biomarker Study in Children and Adolescents

November 24, 2025 updated by: Duke University

New Daily Persistent Headache (NDPH): Biomarker Study and Therapy in Children and Adolescents

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

38

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

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

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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
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)
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
treatment with CGRP antibody for 4 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Calcitonin Gene Related Peptide (CGRP) levels in blood
Time Frame: baseline and 4 months
biomarker
baseline and 4 months
Change in Pituitary Adenylate Cyclase-activating Peptide (PACAP) levels in blood
Time Frame: baseline and 4 months
protein biomarker
baseline and 4 months
Change in Brain derived Neurotrophic factor (BDNF) levels in blood
Time Frame: baseline and 4 months
protein biomarker
baseline and 4 months
Change in Nerve Growth Factor (NGF) levels in blood
Time Frame: baseline and 4 months
protein biomarker
baseline and 4 months
Change in Tumor Necrosis Factor alpha levels in blood
Time Frame: baseline and 4 months
protein biomarker
baseline and 4 months
Change in Vaso Intestinal peptide(VIP) levels in blood
Time Frame: baseline and 4 months
protein biomarker
baseline and 4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disability Scoring
Time Frame: 0 to 4 months
Changes in the Disability Scoring using the Pediatric Migraine Disability Assessment(PedMIDAS) will be recorded at the baseline visit (prior to first CGRP-AB treatment) and 4 months after receiving CGRP-AB treatment. Disability Grade ; 0 to 10. Little to none ; 11 to 30. Mild ; 31 to 50. Moderate ; Greater than 50. Severe
0 to 4 months
Change in Headache frequency
Time Frame: 0 to 4 months
Self-reported headache frequency will be recorded as the number of headaches in the prior month, collected at baseline and 4 months after last CGRP-AB treatment. The patients will be encouraged to keep a headache diary.
0 to 4 months
Screen for Child Anxiety Related Disorders (SCARED)
Time Frame: at enrollment
41 items and 5 factors that parallel the DSM-IV classification of anxiety disorders. A total score of 0-9, normal or no anxiety; 10-18, mild to moderate anxiety; 19-29, moderate to severe anxiety; and 30-63, severe anxiety.
at enrollment
Patient Health Questionnaire-9 modified for Adolescents administered after recruitment
Time Frame: at enrollment
Scores of 0-4 points normal or minimal depression, 5-9 mild depression, 10-14 moderate depression, 15-19 moderately severe depression and 20-27 severe depression
at enrollment
Change in Headache Pain Intensity
Time Frame: 0 to 4 months
Average severity will be measured using a 10-point pain scale, where a higher score indicates greater pain.
0 to 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

International Headache Society

Investigators

  • Principal Investigator: Klaus Werner, MD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 15, 2024

Primary Completion (Actual)

May 29, 2025

Study Completion (Actual)

May 29, 2025

Study Registration Dates

First Submitted

August 24, 2023

First Submitted That Met QC Criteria

August 29, 2023

First Posted (Actual)

August 30, 2023

Study Record Updates

Last Update Posted (Actual)

December 1, 2025

Last Update Submitted That Met QC Criteria

November 24, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00113907

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on New Persistent Daily Headache

Clinical Trials on CGRP antibody

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guatemala

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe