Endogenous Modulation and Central Sensitization in New Daily Persistent Headache ( NDPH ) in Children (EMCS-NDPH)

• ClinicalTrials.gov Identifier: NCT03447782
• Recruitment Status: Completed
• First Posted: February 27, 2018
• Results First Posted: May 6, 2022
• Last Update Posted: May 6, 2022
• Sponsor: Boston Children's Hospital
• Information provided by (Responsible Party): Alyssa Lebel, MD, Boston Children's Hospital

Tracking Information

• First Submitted Date: February 21, 2018
• First Posted Date: February 27, 2018
• Results First Submitted Date: March 7, 2022
• Results First Posted Date: May 6, 2022
• Last Update Posted Date: May 6, 2022
• Actual Study Start Date: July 23, 2018
• Actual Primary Completion Date: November 20, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2022)

Pain Intensity [ Time Frame: 3 months ]

1. A change in pain intensity scores and headache frequency from visit 1 (V1) compared to visit 4 (V4) for NDPH patients after naltrexone has been administered for approximately 3 months. The NRS (numerical rating scale) will be used, with a pain score between 0 to 10, with 0 being no pain and 10 being worst pain imaginable.

Original Primary Outcome Measures (submitted: February 21, 2018)

Pain Intensity [ Time Frame: 3 months ]

1. A change in pain intensity scores and headache frequency- The NRS, numerical rating scale will be used, with a pain score between 0 to 10, with 0 being no pain and 10 being worst pain imaginable, for NDPH patients, chronic and recovered, completing 3 months of naltrexone, as compared to a cohort of patients with NDPH on standard treatment.

Current Secondary Outcome Measures (submitted: April 5, 2022)

• Functional Disability [ Time Frame: 3 months ]
  1. A change in functional disability scores - The functional disability inventory (FDI) will be used to assess differences in disability pre- and post-naltrexone treatment for NDPH patients The FDI is a valid and reliable measure consisting of 15 items concerning perceptions of physical and psychosocial function. Total scores range from 0 to 60, with higher scores indicating greater disability.
• Self- Perceived Pain Sensitivity [ Time Frame: 3 months ]
  A change in self-perceived pain sensitivity - The Pain Sensitivity Questionnaire (PSQ) will be used to assess differences in pain sensitivity pre- and post-naltrexone treatment, as well as between persistent patients and healthy controls. The Pain Sensitivity Questionnaire (PSQ) PSQ is a valid 17 item self-report measure of pain sensitivity. Each item is rated on a scale of 0 to 10, with 0 being no pain and 10 being worst pain imaginable. The PSQ will be used to assess differences in pain sensitivity pre- and post-naltrexone treatment, as well as between recovered and persistent patients.

Original Secondary Outcome Measures (submitted: February 21, 2018)

• Functional disability [ Time Frame: 3 months ]
  1. A change in functional disability scores - The functional disability inventory (FDI) will be used to assess differences in disability pre- and post-naltrexone treatment, as well as between recovered and persistent patients.
• Self- Perceived Pain Sensitivity [ Time Frame: 3 months ]
  A change in self-perceived pain sensitivity - The Pain Sensitivity Questionnaire (PSQ) will be used to assess differences in pain sensitivity pre- and post-naltrexone treatment, as well as between recovered and persistent patients.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Endogenous Modulation and Central Sensitization in New Daily Persistent Headache ( NDPH ) in Children
• Official Title: Endogenous Modulation and Central Sensitization in New Daily Persistent Headache ( NDPH ) in Children

Brief Summary

New daily persistent headache (NDPH) is a primary headache disorder characterized by the daily and unremitting headache pain patients experience with a distinct onset. Despite the known significant impairment associated with NDPH, the process by which some patients with NDPH recover within months while others do not is unknown.

The investigators propose to refine the clinical definition and suggest a novel mechanism underlying new daily persistent headache (NDPH) in adolescents. They further aim to investigate low-dose naltrexone for the treatment of new daily persistent headache. Healthy controls will also be enrolled in order to investigate the existence of a biomarker for NDPH. Adolescents ages 10-17 will be recruited from Boston Children's Hospital Pediatric Headache Program.

Detailed Description

The purpose of this study is to investigate low-dose naltrexone for the treatment of new daily persistent headache (NDPH) in adolescents ages 10-17. New daily persistent headache (NDPH) is a primary headache disorder characterized by continuous pain experienced for at least 3 months from distinct onset. Patients with NDPH have compromised academic performance, school absence, anxiety, depressed mood, sleep impairment, family disruption, and high health care costs. Despite the known significant impairment associated with NDPH, the process by which some patients with NDPH recover within months while others do not is unknown. With the goal of enhancing the clinical definition of NDPH, investigators will describe differences between patients with NDPH and healthy controls.

Additionally, little is known about which medications effectively manage and treat NDPH. One proposed medication that may benefit children and adolescents with NDPH is low-dose naltrexone. Naltrexone is an anti-inflammatory agent, similar to the opioid antagonist naloxone. Naltrexone is an effective treatment for opioid addiction, however, it was recently discovered that when taken in low doses (1/10 of the typical dose) naltrexone is capable of reducing the severity of chronic pain symptoms. By acting on glial cells in the nervous system as well as other receptors in the brain, naltrexone is capable of exerting analgesic effects. With this analgesic property, it has been speculated that low-dose naltrexone may be an effective treatment for the management of several chronic pain conditions, including headache.

Although more research must be conducted to evaluate long-term effects of using low-dose naltrexone, prior studies show that there are little short-term consequences associated with using this drug as a form of treatment for chronic pain symptoms. Investigators aim to assess the efficacy and safety of low-dose naltrexone in the treatment of patients with NDPH.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This group includes patients reviewed after 3 months of observational study with NDPH who have not improved clinically-they will take naltrexone, 4.5 mg, for 3 months. The other group includes healthy control patients

Masking: None (Open Label)
Primary Purpose: Diagnostic

• Condition: New Daily Persistent Headache (NDPH)

Intervention

Drug: Naltrexone HCl (Bulk) Powder

For the NDPH Persistent group, patient will take naltrexone, 4.5 mg, po 1 time/day for three months-Naltrexone will be compounded from Naltrexone HCL powder

Study Arms

• Experimental: NDPH Persistent

  Patients will be evaluated in clinic 1 month after the phone call evaluation. At this time, patients will begin a 3 month trial of low-dose naltrexone (Naltrexone HCL powder compounded to provide 4.5mg once per day orally).

  Patients will be evaluated in clinic 3 months after beginning treatment with naltrexone.

  Intervention: Drug: Naltrexone HCl (Bulk) Powder
• No Intervention: Healthy Controls
  These participants will be in the research study for the initial visit only. They will be evaluated by a physician or nurse practitioner

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 7, 2022): 45
• Original Estimated Enrollment (submitted: February 21, 2018): 150
• Actual Study Completion Date: November 20, 2020
• Actual Primary Completion Date: November 20, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1) Patients meeting clinical International Classification of Headache Disorders (ICHD-3 )classification for NDPH 2) Age 10-17 years, all sexes, races, and ethnicities 3) English speaking 4) Able to wean off headache prophylactic medication 2 weeks prior to start of Naltrexone trial (patient will still be able to use abortive medication throughout the duration of the study) 5) On stable psychotropic medication for mild anxiety and/or mood disturbance for 2 weeks

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Exclusion Criteria:

1) Children and adolescents with significant chronic medical illness: Central Nervous systen (secondary headache disorder other than mild traumatic brain injury); Cardiac, Pulmonary other than stable asthma, Metabolic, Renal, Hepatic 2) Significant psychiatric disorder, such as major depression, somatization disorder, and psychosis 3) Pregnancy 4) Intellectual delay or cognitive limitations precluding completion of questionnaires or following instructions.

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Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 17 Years (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03447782
• Other Study ID Numbers: P00026929
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Alyssa Lebel, MD, Boston Children's Hospital
• Original Responsible Party: Alyssa Lebel, MD, Boston Children's Hospital, Director, Chronic Headache Program, BCH; Associate Professor of Anesthesiology, HMS
• Current Study Sponsor: Boston Children's Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Alyssa Lebel, MD; Boston Children's Hospital

• PRS Account: Boston Children's Hospital
• Verification Date: April 2022