New Daily Persistent Headache (NDPH)
Conditions
Keywords
New Daily Persistent Headache, Chronic Headache
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.
Interventions
DRUGNaltrexone 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
Sponsors
Boston Children's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
Yes
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 \-
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Disability | 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 | 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. |
Countries
United States
Participant flow
Pre-assignment details
No healthy controls were able to be recruited as the COVID-19 pandemic caused the study to shut down.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | NDPH Persistent |
|---|---|
| Age, Categorical <=18 years | 45 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 15.7 years STANDARD_DEVIATION 1.32 |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Native American or Alaskan Native | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized Unknown | 7 Participants |
| Race/Ethnicity, Customized White or Caucasian | 36 Participants |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 38 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 45 |
| other Total, other adverse events | 0 / 45 |
| serious Total, serious adverse events | 0 / 45 |
Outcome results
Primary
Pain Intensity
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.
Time frame: 3 months
Population: The healthy control arm was not included here because COVID-19 necessitated the shut-down of this protocol and no healthy controls were able to be recruited.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NDPH Persistent | Pain Intensity | V1 Pain Rating | 5.82 score on a scale | Standard Deviation 1.47 |
| NDPH Persistent | Pain Intensity | V4 Pain Rating | 4.92 score on a scale | Standard Deviation 1.64 |
Secondary
Functional Disability
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.
Time frame: 3 months
Population: The healthy control arm was not included here because COVID-19 necessitated the shut-down of this protocol and no healthy controls were able to be recruited.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NDPH Persistent | Functional Disability | FDI V1 | 15.16 score on a scale | Standard Deviation 8.56 |
| NDPH Persistent | Functional Disability | FDI V4 | 10.96 score on a scale | Standard Deviation 8.46 |
Secondary
Self- Perceived Pain Sensitivity
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.
Time frame: 3 months
Population: The healthy control arm was not included here because COVID-19 necessitated the shut-down of this protocol and no healthy controls were able to be recruited.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NDPH Persistent | Self- Perceived Pain Sensitivity | PSQ total V1 | 3.21 units on a scale | Standard Deviation 1.03 |
| NDPH Persistent | Self- Perceived Pain Sensitivity | PSQ total V4 | 3.22 units on a scale | Standard Deviation 1.5 |