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Low Dose Naltrexone for Chronic Pain From Arthritis (LDN-VA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03008590
Recruitment Status : Completed
First Posted : January 2, 2017
Results First Posted : March 3, 2021
Last Update Posted : March 3, 2021
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Osteoarthritis
Arthritis, Rheumatoid
Arthritis, Psoriatic
Interventions Drug: Naltrexone
Drug: Placebo
Enrollment 29
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Naltrexone First Then Placebo Placebo First Then Naltrexone
Hide Arm/Group Description

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 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

Period Title: Overall Study
Started 14 15
Completed 11 12
Not Completed 3 3
Arm/Group Title Naltrexone First Placebo First Total
Hide Arm/Group Description Received naltrexone first, then placebo Received placebo first, then naltrexone Total of all reporting groups
Overall Number of Baseline Participants 11 12 23
Hide Baseline Analysis Population Description
Patients who completed the study
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 12 participants 23 participants
62  (8.2) 64  (11.9) 63  (10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 23 participants
Female
1
   9.1%
3
  25.0%
4
  17.4%
Male
10
  90.9%
9
  75.0%
19
  82.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 23 participants
Hispanic or Latino
1
   9.1%
0
   0.0%
1
   4.3%
Not Hispanic or Latino
10
  90.9%
12
 100.0%
22
  95.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 23 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  18.2%
1
   8.3%
3
  13.0%
White
9
  81.8%
11
  91.7%
20
  87.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 11 participants 12 participants 23 participants
11
 100.0%
12
 100.0%
23
 100.0%
Diagnosis, OA or IA  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 12 participants 23 participants
Osteoarthritis
7
  63.6%
10
  83.3%
17
  73.9%
Inflammatory arthritis
4
  36.4%
2
  16.7%
6
  26.1%
Body mass index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 11 participants 12 participants 23 participants
33  (7.9) 35  (6.9) 34  (7.3)
Brief Pain Inventory - Pain interference (sum of 7 subscales, each 0-10)  
Mean (Standard Deviation)
Unit of measure:  Units on a 0-70 scale (higher is worse)
Number Analyzed 11 participants 12 participants 23 participants
39  (9.5) 42  (11.5) 41  (10.5)
Brief Pain Inventory - Pain severity  
Mean (Standard Deviation)
Unit of measure:  Units on a 0-10 scale (higher is worse)
Number Analyzed 11 participants 12 participants 23 participants
5.9  (1.2) 5.9  (1.3) 5.9  (1.2)
1.Primary Outcome
Title Brief Pain Inventory - Pain Interference
Hide Description 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.
Time Frame 8 and 16 weeks, ie after 8 weeks naltrexone or 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
-23  (19.4) -22  (19.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection At End of 8 Weeks Naltrexone Treatment, At End of 8 Weeks Placebo Treatment
Comments Data from the primary or secondary outcome measures were the dependent variables. The patient was the random effect. Dependent fixed effects variables included treatment at the time of data collection (naltrexone or placebo), group (naltrexone first or placebo first), and week (4, 8, 12, and 16).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.90
Comments Significance pre-specified at P<0.05
Method Mixed Models Analysis
Comments [Not Specified]
2.Secondary Outcome
Title Brief Pain Inventory - Pain Severity
Hide Description 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.
Time Frame 8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.7  (1.87) -2.0  (2.17)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection At End of 8 Weeks Naltrexone Treatment, At End of 8 Weeks Placebo Treatment
Comments Data from the primary or secondary outcome measures were the dependent variables. The patient was the random effect. Dependent fixed effects variables included treatment at the time of data collection (naltrexone or placebo), group (naltrexone first or placebo first), and week (4, 8, 12, and 16).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.22
Comments Significance pre-specified at P<0.05
Method Mixed Models Analysis
Comments [Not Specified]
3.Secondary Outcome
Title painDETECT
Hide Description 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.
Time Frame 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
-4.0  (6.26) -5.6  (5.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection At End of 8 Weeks Naltrexone Treatment, At End of 8 Weeks Placebo Treatment
Comments Data from the primary or secondary outcome measures were the dependent variables. The patient was the random effect. Dependent fixed effects variables included treatment at the time of data collection (naltrexone or placebo), group (naltrexone first or placebo first), and week (4, 8, 12, and 16).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments Although significance was pre-specified at P<0.05, it is suspected that this result is spurious due to multiple comparisons
Method Mixed Models Analysis
Comments [Not Specified]
4.Secondary Outcome
Title Brief Fatigue Inventory
Hide Description 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.
Time Frame 8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.8  (1.61) -1.8  (2.71)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection At End of 8 Weeks Naltrexone Treatment, At End of 8 Weeks Placebo Treatment
Comments Data from the primary or secondary outcome measures were the dependent variables. The patient was the random effect. Dependent fixed effects variables included treatment at the time of data collection (naltrexone or placebo), group (naltrexone first or placebo first), and week (4, 8, 12, and 16).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3
Comments Significance pre-specified at P<0.05
Method Mixed Models Analysis
Comments [Not Specified]
5.Secondary Outcome
Title Beck Depression Inventory-II
Hide Description 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
Time Frame 8 and16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.0  (4.29) -1.7  (6.04)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection At End of 8 Weeks Naltrexone Treatment, At End of 8 Weeks Placebo Treatment
Comments Data from the primary or secondary outcome measures were the dependent variables. The patient was the random effect. Dependent fixed effects variables included treatment at the time of data collection (naltrexone or placebo), group (naltrexone first or placebo first), and week (4, 8, 12, and 16).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.04
Comments Although significance was pre-specified at P<0.05, it is suspected that this result is spurious due to multiple comparisons
Method Mixed Models Analysis
Comments [Not Specified]
6.Secondary Outcome
Title Clinical Global Impression of Severity (CGI-S)
Hide Description 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.
Time Frame 8 and16 weeks, ie after 8 weeks naltrexone and 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.1  (1.59) -1.1  (1.83)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection At End of 8 Weeks Naltrexone Treatment, At End of 8 Weeks Placebo Treatment
Comments Data from the primary or secondary outcome measures were the dependent variables. The patient was the random effect. Dependent fixed effects variables included treatment at the time of data collection (naltrexone or placebo), group (naltrexone first or placebo first), and week (4, 8, 12, and 16).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments Significance pre-specified at P<0.05
Method Mixed Models Analysis
Comments [Not Specified]
7.Secondary Outcome
Title Clinical Global Impression of Improvement (CGI-I)
Hide Description 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.
Time Frame 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 23 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.3  (1.2) -0.2  (1.71)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection At End of 8 Weeks Naltrexone Treatment, At End of 8 Weeks Placebo Treatment
Comments Data from the primary or secondary outcome measures were the dependent variables. The patient was the random effect. Dependent fixed effects variables included treatment at the time of data collection (naltrexone or placebo), group (naltrexone first or placebo first), and week (4, 8, 12, and 16).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.92
Comments Significance pre-specified at P<0.05
Method Mixed Models Analysis
Comments [Not Specified]
8.Secondary Outcome
Title Patient Reported Outcomes Measurement Information System Profile (PROMIS-29)
Hide Description 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.
Time Frame 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Data not collected
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title C Reactive Protein (CRP)
Hide Description 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.
Time Frame 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
10.Secondary Outcome
Title Disease Activity Score (DAS28)
Hide Description 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.
Time Frame 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Data not collected.
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
11.Secondary Outcome
Title Bath Ankylosing Spondylitis Activity Index (BASDAI)
Hide Description 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.
Time Frame 8 and 16 weeks, ie after 8 weeks naltrexone and after 8 weeks placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Data not collected
Arm/Group Title At End of 8 Weeks Naltrexone Treatment At End of 8 Weeks Placebo Treatment
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 16 weeks (8 weeks each naltrexone and placebo)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title During Naltrexone Treatment During Placebo Treatment
Hide Arm/Group Description Adverse events during naltrexone Adverse events during placebo
All-Cause Mortality
During Naltrexone Treatment During Placebo Treatment
Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)      0/29 (0.00%)    
Hide Serious Adverse Events
During Naltrexone Treatment During Placebo Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/29 (0.00%)      2/29 (6.90%)    
Infections and infestations     
Anaplasmosis *  0/29 (0.00%)  0 1/29 (3.45%)  1
Respiratory, thoracic and mediastinal disorders     
Shortness of breath * [1]  0/29 (0.00%)  0 1/29 (3.45%)  1
*
Indicates events were collected by non-systematic assessment
[1]
Shortness of breath of unknown origin, led to hospitalization, resolved
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
During Naltrexone Treatment During Placebo Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/29 (24.14%)      12/29 (41.38%)    
Gastrointestinal disorders     
Abdominal / GI symptoms * [1]  0/29 (0.00%)  0 3/29 (10.34%)  3
General disorders     
Fatigue *  1/29 (3.45%)  1 2/29 (6.90%)  2
Immune system disorders     
Lip and tongue swelling * [2]  1/29 (3.45%)  1 0/29 (0.00%)  0
Infections and infestations     
Infections, minor viral or bacterial *  1/29 (3.45%)  1 5/29 (17.24%)  5
Musculoskeletal and connective tissue disorders     
Ankle injury *  1/29 (3.45%)  1 0/29 (0.00%)  0
Nervous system disorders     
Dizziness *  2/29 (6.90%)  2 0/29 (0.00%)  0
Renal and urinary disorders     
Reduced renal function * [3]  0/29 (0.00%)  0 1/29 (3.45%)  1
Skin and subcutaneous tissue disorders     
Dermatitis * [4]  1/29 (3.45%)  1 1/29 (3.45%)  1
*
Indicates events were collected by non-systematic assessment
[1]
Nausea, vomiting, bloating
[2]
Suspected allergic reaction
[3]
Mild, transient reduction in GFR, unknown cause
[4]
One case poison ivy, another unknown, both resolved
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Paul Monach, Chief, Rheumatology Section
Organization: VA Boston Healthcare System
Phone: 857-364-5552
EMail: Paul.Monach@va.gov
Layout table for additonal information
Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03008590    
Other Study ID Numbers: NURB-008-16S
First Submitted: December 22, 2016
First Posted: January 2, 2017
Results First Submitted: December 23, 2020
Results First Posted: March 3, 2021
Last Update Posted: March 3, 2021