NDPH Biomarker Study in Children and Adolescents

Study Overview
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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 12-18 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.

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

Conditions
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New Persistent Daily Headache

Intervention / Treatment
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* Drug: CGRP antibody


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients between 12-18 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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NPDH (New Persistent Daily Headache)<br>Patients with new persistent daily headache (NDPH) ages 12-18 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<br>* treatment with CGRP antibody for 4 months<br>|
| Healthy (Normal) Controls<br>Children with normal development, aged 12-18 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<br>Patients between 12-18 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<br>* treatment with CGRP antibody for 4 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disability Scoring | 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 | 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) | 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 | 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 | Average severity will be measured using a 10-point pain scale, where a higher score indicates greater pain. | 0 to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NPDH CGRP PACAP BDNF NGF TNF-alpha VIP