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

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: New Daily Persistent Headache (NDPH)
• Intervention: Drug: Naltrexone HCl (Bulk) Powder
• Enrollment: 45

Participant Flow

Recruitment Details
Pre-assignment Details	No healthy controls were able to be recruited as the COVID-19 pandemic caused the study to shut down.

Arm/Group Title	NDPH Persistent
Arm/Group Description	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
Period Title: Overall Study
Started	45
Completed	25
Not Completed	20

Baseline Characteristics

Arm/Group Title		NDPH Persistent
Arm/Group Description		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
Overall Number of Baseline Participants		45
Baseline Analysis Population Description		The healthy control arm was not included here as COVID-19 necessitated the shut-down of this study and no healthy controls were able to be recruited.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	<=18 years	45 100.0%
	Between 18 and 65 years	0 0.0%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	45 participants
		15.7 (1.32)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	45 participants
	Female	38 84.4%
	Male	7 15.6%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	45 participants
White or Caucasian		36 80.0%
Other		2 4.4%
Black or African American		0 0.0%
Asian		0 0.0%
Native Hawaiian or Other Pacific Islander		0 0.0%
Native American or Alaskan Native		0 0.0%
Unknown		7 15.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	45 participants
		45

Outcome Measures

1. Primary Outcome

Title	Pain Intensity
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	NDPH Persistent
Arm/Group Description:	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
Overall Number of Participants Analyzed	25
Mean (Standard Deviation); Unit of Measure: score on a scale
V1 Pain Rating	5.82 (1.47)
V4 Pain Rating	4.92 (1.64)

2. Secondary Outcome

Title	Functional Disability
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	NDPH Persistent
Arm/Group Description:	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
Overall Number of Participants Analyzed	25
Mean (Standard Deviation); Unit of Measure: score on a scale
FDI V1	15.16 (8.56)
FDI V4	10.96 (8.46)

3. Secondary Outcome

Title	Self- Perceived Pain Sensitivity
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	NDPH Persistent
Arm/Group Description:	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
Overall Number of Participants Analyzed	25
Mean (Standard Deviation); Unit of Measure: units on a scale
PSQ total V1	3.21 (1.03)
PSQ total V4	3.22 (1.50)

Adverse Events

Time Frame	4-7 months
Adverse Event Reporting Description	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/Group Title	NDPH Persistent
Arm/Group Description	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
All-Cause Mortality
	NDPH Persistent
	Affected / at Risk (%)
Total	0/45 (0.00%)
Serious Adverse Events
	NDPH Persistent
	Affected / at Risk (%)
Total	0/45 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	NDPH Persistent
	Affected / at Risk (%)
Total	0/45 (0.00%)

Limitations and Caveats

This trial had to shut down due to the emergence of the COVID-19 virus in 2020. Because of this, our sample size is smaller than anticipated and thus serves as a limitation of our trial. Additionally, healthy controls were extremely difficult to recruit for the study given the COVID-19 pandemic and thus we were unable to adequately compare NDPH patients to healthy controls.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Alyssa Lebel
• Organization: Boston Children's Hospital
• Phone: 7812161960
• EMail: alyssa.lebel@childrens.harvard.edu

• Responsible Party: Alyssa Lebel, MD, Boston Children's Hospital
• ClinicalTrials.gov Identifier: NCT03447782
• Other Study ID Numbers: P00026929
• First Submitted: February 21, 2018
• First Posted: February 27, 2018
• Results First Submitted: March 7, 2022
• Results First Posted: May 6, 2022
• Last Update Posted: May 6, 2022