Trial Outcomes & Findings for Low Dose Naltrexone for Chronic Pain From Arthritis (NCT NCT03008590)

NCT ID: NCT03008590

Last Updated: 2021-03-03

Results Overview

Sum of 7 questions (each on a 0-10 scale, therefore 0-70 total) on how much pain has interfered with general function, walking ability, mood, normal work, relations with other people, sleep, and enjoyment of life. Higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks of naltrexone, or after 8 weeks of placebo.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 29 participants
• Primary outcome timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone or 8 weeks placebo
• Results posted on: 2021-03-03

Participant Flow

Participant milestones

Measure	Naltrexone First Then Placebo Naltrexone for 8 weeks, then placebo for 8 weeks, blinded cross-over design Naltrexone: One 4.5 mg capsule each evening Placebo: One capsule each evening	Placebo First Then Naltrexone Placebo for 8 weeks, then naltrexone for 8 weeks, blinded cross-over design Naltrexone: One 4.5 mg capsule each evening Placebo: One capsule each evening
Overall Study STARTED	14	15
Overall Study COMPLETED	11	12
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Low Dose Naltrexone for Chronic Pain From Arthritis

Baseline characteristics by cohort

Measure	Naltrexone First n=11 Participants Received naltrexone first, then placebo	Placebo First n=12 Participants Received placebo first, then naltrexone	Total n=23 Participants Total of all reporting groups
Age, Continuous	62 years STANDARD_DEVIATION 8.2 • n=5 Participants	64 years STANDARD_DEVIATION 11.9 • n=7 Participants	63 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Diagnosis, OA or IA Osteoarthritis	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Diagnosis, OA or IA Inflammatory arthritis	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Body mass index	33 kg/m^2 STANDARD_DEVIATION 7.9 • n=5 Participants	35 kg/m^2 STANDARD_DEVIATION 6.9 • n=7 Participants	34 kg/m^2 STANDARD_DEVIATION 7.3 • n=5 Participants
Brief Pain Inventory - Pain interference (sum of 7 subscales, each 0-10)	39 units on a 0-70 scale (higher is worse) STANDARD_DEVIATION 9.5 • n=5 Participants	42 units on a 0-70 scale (higher is worse) STANDARD_DEVIATION 11.5 • n=7 Participants	41 units on a 0-70 scale (higher is worse) STANDARD_DEVIATION 10.5 • n=5 Participants
Brief Pain Inventory - Pain severity	5.9 units on a 0-10 scale (higher is worse) STANDARD_DEVIATION 1.2 • n=5 Participants	5.9 units on a 0-10 scale (higher is worse) STANDARD_DEVIATION 1.3 • n=7 Participants	5.9 units on a 0-10 scale (higher is worse) STANDARD_DEVIATION 1.2 • n=5 Participants

PRIMARY outcome

Timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone or 8 weeks placebo

Sum of 7 questions (each on a 0-10 scale, therefore 0-70 total) on how much pain has interfered with general function, walking ability, mood, normal work, relations with other people, sleep, and enjoyment of life. Higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks of naltrexone, or after 8 weeks of placebo.

Outcome measures

Measure	At End of 8 Weeks Naltrexone Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.	At End of 8 Weeks Placebo Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.
Brief Pain Inventory - Pain Interference	-23 units on a scale Standard Deviation 19.4	-22 units on a scale Standard Deviation 19.2

SECONDARY outcome

Timeframe: 8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Average severity of pain in the past 7 days (0-10). Higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks naltrexone, and after 8 weeks placebo.

Outcome measures

Measure	At End of 8 Weeks Naltrexone Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.	At End of 8 Weeks Placebo Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.
Brief Pain Inventory - Pain Severity	-1.7 units on a scale Standard Deviation 1.87	-2.0 units on a scale Standard Deviation 2.17

SECONDARY outcome

Timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Measure of neuropathic pain (0-38). Lower score indicates nociceptive pain, higher score indicates neuropathic pain. Results are reported as change from baseline: after 8 weeks of naltrexone or after 8 weeks placebo.

Outcome measures

Measure	At End of 8 Weeks Naltrexone Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.	At End of 8 Weeks Placebo Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.
painDETECT	-4.0 units on a scale Standard Deviation 6.26	-5.6 units on a scale Standard Deviation 5.73

SECONDARY outcome

Timeframe: 8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Questionnaire, severity of fatigue and fatigue's interference with activity (0-10 scales). Higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks naltrexone or after 8 weeks placebo.

Outcome measures

Measure	At End of 8 Weeks Naltrexone Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.	At End of 8 Weeks Placebo Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.
Brief Fatigue Inventory	-1.8 units on a scale Standard Deviation 1.61	-1.8 units on a scale Standard Deviation 2.71

SECONDARY outcome

Timeframe: 8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Questionnaire measuring severity of depression (0-69). Used primarily during screening to exclude enrollment of patients with severe depression, but also as a safety outcome measure during the study. Higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks of naltrexone, or after 8 weeks of placebo

Outcome measures

Measure	At End of 8 Weeks Naltrexone Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.	At End of 8 Weeks Placebo Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.
Beck Depression Inventory-II	-1.0 units on a scale Standard Deviation 4.29	-1.7 units on a scale Standard Deviation 6.04

SECONDARY outcome

Timeframe: 8 and16 weeks, ie after 8 weeks naltrexone and 8 weeks placebo

7-point scale (1-7) of patients' self-reporting of severity during the study. Higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks naltrexone, or after 8 weeks placebo.

Outcome measures

Measure	At End of 8 Weeks Naltrexone Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.	At End of 8 Weeks Placebo Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.
Clinical Global Impression of Severity (CGI-S)	-1.1 units on a scale Standard Deviation 1.59	-1.1 units on a scale Standard Deviation 1.83

SECONDARY outcome

Timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

7-point scale (1-7) of patients' self-reporting of improvement or worsening during the study. A higher score is a worse outcome. Results are reported as change from baseline: after 8 weeks naltrexone, or after 8 weeks placebo.

Outcome measures

Measure	At End of 8 Weeks Naltrexone Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.	At End of 8 Weeks Placebo Treatment n=23 Participants Data from naltrexone periods were pooled for presentation purposes, but period (first or second) was included as a variable in the statistical analysis. Results shown are change from baseline.
Clinical Global Impression of Improvement (CGI-I)	-0.3 units on a scale Standard Deviation 1.2	-0.2 units on a scale Standard Deviation 1.71

SECONDARY outcome

Timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Population: Data not collected

Questionnaire, survey of 29 questions assessing health-related quality of life across 8 domains. The subscores are not added to give a single score. Results would have been reported as change from baseline (after 8 weeks naltrexone, or after 8 weeks placebo), but data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Population: Data were not collected

Blood test for inflammation. Plan was to reported as change from baseline (after 8 weeks naltrexone, or after 8 weeks placebo), but data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Population: Data not collected.

Measure of disease activity in rheumatoid arthritis. Plan was to reported report results as change from baseline (after 8 weeks naltrexone, or after 8 weeks placebo), but data were not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo

Population: Data not collected

Patient-reported index of disease activity for ankylosing spondylitis. Higher is more severe. Results would have been reported as change from baseline (after 8 weeks naltrexone, or after 8 weeks placebo) but data were not collected.

Outcome measures

Outcome data not reported

Adverse Events

During Naltrexone Treatment

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

During Placebo Treatment

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	During Naltrexone Treatment n=29 participants at risk Adverse events during naltrexone	During Placebo Treatment n=29 participants at risk Adverse events during placebo
Infections and infestations Anaplasmosis	0.00% 0/29 • 16 weeks (8 weeks each naltrexone and placebo)	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/29 • 16 weeks (8 weeks each naltrexone and placebo)	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)

Other adverse events

Measure	During Naltrexone Treatment n=29 participants at risk Adverse events during naltrexone	During Placebo Treatment n=29 participants at risk Adverse events during placebo
General disorders Fatigue	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)	6.9% 2/29 • Number of events 2 • 16 weeks (8 weeks each naltrexone and placebo)
Nervous system disorders Dizziness	6.9% 2/29 • Number of events 2 • 16 weeks (8 weeks each naltrexone and placebo)	0.00% 0/29 • 16 weeks (8 weeks each naltrexone and placebo)
Infections and infestations Infections, minor viral or bacterial	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)	17.2% 5/29 • Number of events 5 • 16 weeks (8 weeks each naltrexone and placebo)
Gastrointestinal disorders Abdominal / GI symptoms	0.00% 0/29 • 16 weeks (8 weeks each naltrexone and placebo)	10.3% 3/29 • Number of events 3 • 16 weeks (8 weeks each naltrexone and placebo)
Immune system disorders Lip and tongue swelling	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)	0.00% 0/29 • 16 weeks (8 weeks each naltrexone and placebo)
Skin and subcutaneous tissue disorders Dermatitis	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)
Renal and urinary disorders Reduced renal function	0.00% 0/29 • 16 weeks (8 weeks each naltrexone and placebo)	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)
Musculoskeletal and connective tissue disorders Ankle injury	3.4% 1/29 • Number of events 1 • 16 weeks (8 weeks each naltrexone and placebo)	0.00% 0/29 • 16 weeks (8 weeks each naltrexone and placebo)

Additional Information

Dr Paul Monach, Chief, Rheumatology Section

VA Boston Healthcare System

Phone: 857-364-5552

Email: Paul.Monach@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place