Trial Outcomes & Findings for Low-Dose Naltrexone (LDN) for Depression Relapse and Recurrence (NCT NCT01874951)
NCT ID: NCT01874951
Last Updated: 2017-02-24
Results Overview
Hamilton Depression Scale-17 (HAM-D-17) item. The change in scores depends on the difference between the initial (baseline) score and the final score at the conclusion of the double blind treatment period. There is no formal range of score changes, since they depend on the initial and final score. A negative score represents a lowering in the score from baseline to end (improvement), and a positive score indicates an increase in score from baseline to end (worsening). A zero score would indicate no change. In theory, the maximum drop in score would be from 52 to zero, or -52. A maximum increase would be from 18 (the minimum score required for admission) to 52, or +34.
COMPLETED
PHASE2
12 participants
Change from baseline to week 3
2017-02-24
Participant Flow
After approval by our Institutional Review Board (IRB), written informed consent was obtained. Boston area men and women with major depressive disorder (MDD) were recruited from 01/13/2014-11/11/2014 via IRB-approved newspaper, television, internet, and radio ads initiated by Massachusetts General Hospital (MGH) and Boston Clinical Trials (BCT).
21 prospective subjects were screened. The following were excluded: sub-threshold Hamilton-D (HAMD) scores (n=3); too recent changes in medication regimen (n=2); cerebrovascular accident in past 5 years (n=1); no history of past treatment response (n=1); inappropriate antidepressant (n=1); antidepressant dose too low and duration too short (n=1).
Participant milestones
| Measure |
Placebo
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Low-Dose Naltrexone (LDN) for Depression Relapse and Recurrence
Baseline characteristics by cohort
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
43 years
STANDARD_DEVIATION 11 • n=5 Participants
|
47 years
STANDARD_DEVIATION 13 • n=7 Participants
|
45 years
STANDARD_DEVIATION 12 • n=5 Participants
|
|
Gender
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Gender
Male
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Hamilton-D-17 score
|
23.7 units on a scale
STANDARD_DEVIATION 2.3 • n=5 Participants
|
21.2 units on a scale
STANDARD_DEVIATION 2.0 • n=7 Participants
|
22.4 units on a scale
STANDARD_DEVIATION 2.4 • n=5 Participants
|
|
Hamilton-D-28 score
|
26.3 units on a scale
STANDARD_DEVIATION 2.6 • n=5 Participants
|
26.2 units on a scale
STANDARD_DEVIATION 4.0 • n=7 Participants
|
26.3 units on a scale
STANDARD_DEVIATION 3.2 • n=5 Participants
|
|
MADRS-10 score
|
30.7 units on a scale
STANDARD_DEVIATION 4.3 • n=5 Participants
|
30.4 units on a scale
STANDARD_DEVIATION 4.9 • n=7 Participants
|
30.5 units on a scale
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
MADRS-15 score
|
36.7 units on a scale
STANDARD_DEVIATION 4.2 • n=5 Participants
|
36.6 units on a scale
STANDARD_DEVIATION 6.2 • n=7 Participants
|
36.6 units on a scale
STANDARD_DEVIATION 4.9 • n=5 Participants
|
|
Clinical Global Improvement-Severity (CGI-S) score
|
4.3 units on a scale
STANDARD_DEVIATION 0.5 • n=5 Participants
|
4.3 units on a scale
STANDARD_DEVIATION 0.5 • n=7 Participants
|
4.3 units on a scale
STANDARD_DEVIATION 0.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: Change from baseline to week 3Population: Study completers.
Hamilton Depression Scale-17 (HAM-D-17) item. The change in scores depends on the difference between the initial (baseline) score and the final score at the conclusion of the double blind treatment period. There is no formal range of score changes, since they depend on the initial and final score. A negative score represents a lowering in the score from baseline to end (improvement), and a positive score indicates an increase in score from baseline to end (worsening). A zero score would indicate no change. In theory, the maximum drop in score would be from 52 to zero, or -52. A maximum increase would be from 18 (the minimum score required for admission) to 52, or +34.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Change in HAM-D-17 Total Score
|
-5.8 units on a scale
Standard Deviation 5.1
|
-9.5 units on a scale
Standard Deviation 6.9
|
SECONDARY outcome
Timeframe: Change from baseline to week 3Population: Study subjects who completed the protocol
Hamilton Depression Scale-28 item. The change in scores depends on the difference between the initial (baseline) score and the final score at the conclusion of the double blind treatment period. There is no formal range of score changes, since they depend on the initial and final score. A negative score represents a lowering in the score from baseline to end (improvement), and a positive score indicates an increase in score from baseline to end (worsening). A zero score would indicate no change. In theory, the maximum drop in score would be from 81 to zero, or -81. A maximum increase would be from 18 (the minimum score required for admission) to 81, or +63.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Change in HAM-D28 Total Score
|
-6.5 units on a scale
Standard Deviation 7.4
|
-14.6 units on a scale
Standard Deviation 6.7
|
SECONDARY outcome
Timeframe: Change from baseline to week 3Population: Study completers.
Montgomery-Asberg Depression Rating Scale- 10 item. The change in scores depends on the difference between the initial (baseline) score and the final score at the conclusion of the double blind treatment period. There is no formal range of score changes, since they depend on the initial and final score. A negative score represents a lowering in the score from baseline to end (improvement), and a positive score indicates an increase in score from baseline to end (worsening). A zero score would indicate no change. In theory, the maximum drop in score would be from 60 to zero, or -60. There is no minimum score on the MADRS-10 required for study entry, since the HAMD-17 was the sole entry criteria. However, a score of 18 on the HAMD17 corresponds to approximately a score of 21 on the MADRS-10. A maximum estimated increase would thus be from 21 to 60, or +39.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Change in MADRS-10 Total Score
|
-7.8 units on a scale
Standard Deviation 8.5
|
-18.2 units on a scale
Standard Deviation 5.5
|
SECONDARY outcome
Timeframe: Change from baseline to week 3Population: Study completers.
Montgomery-Asberg Depression Rating Scale- 15 item. The change in scores depends on the difference between the initial (baseline) score and the final score at the conclusion of the double blind treatment period. There is no formal range of score changes, since they depend on the initial and final score. A negative score represents a lowering in the score from baseline to end (improvement), and a positive score indicates an increase in score from baseline to end (worsening). A zero score would indicate no change. In theory, the maximum drop in score would be from 90 to zero, or -90. There is no minimum score on the MADRS-15 required for study entry, since the HAMD-17 was the sole entry criteria. However, a score of 18 on the HAMD17 corresponds to approximately a score of 21 on the MADRS-10. A maximum estimated increase would thus be from 21 to 90, or +69.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Change in MADRS-15 Total Score
|
-10.7 units on a scale
Standard Deviation 10
|
-23.4 units on a scale
Standard Deviation 6.8
|
SECONDARY outcome
Timeframe: Change from baseline to week 3Population: Study completers.
Clinical Global Improvement-Severity Scale. The CGI-S score is a one-item scale that measures severity of depression, scored from 1-7, where 1 = no depression is present, 2 = borderline depression, 3 = mild depression, 4 = moderate depression, 5 = marked depression, 6 = severe depression, and 7 = among the most extremely depressed patient. Thus higher scores indicate greater depressive severity. The change in CGI-S score can represent a drop from 7 (maximum severity) to 1 (no depression) or -6. There is no minimum CGI-S score required for admission, but a minimum score of 18 on the HAMD17 corresponds to approximately a score of 4 on the CGI-S. Thus a maximum worsening would be from 4 to 7, or +3.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Change in CGI-S Total Score
|
-0.3 units on a scale
Standard Deviation 0.8
|
-1.3 units on a scale
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: From baseline to week 3Population: Study completers.
Clinical Global Improvement-Improvement Scale. The CGI-I scale is a one item scale that measures overall change in patient's global condition compared to when they were entered into the study. The scale is graded from 1-7, where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. Thus higher scores indicate greater worsening, and lower scores indicate greater improvement. The lowest possible score (indicating maximum improvement) is 1, and the highest possible score (indicating greatest worsening) is 7.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Final CGI-I Score
|
3.5 units on a scale
Standard Deviation 0.8
|
2.2 units on a scale
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: Response rate after 3 weeksPopulation: Study completers.
Response is defined as an improvement in HAM-D-17 score of greater than or equal to 50% compared to baseline score. Response rate is the percent of patients who attain this threshold degree of improvement.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Response Rate
|
1 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Remission rate at 3 weeks.Population: Study completers.
Remission is defined as a final HAM-D-17 score of 7 or less. Remission rate is the percent of patients who attain this threshold score.
Outcome measures
| Measure |
Placebo
n=6 Participants
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 Participants
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Remission Rate
|
0 Participants
|
3 Participants
|
Adverse Events
Placebo
Naltrexone
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=6 participants at risk
In this arm, patients will receive placebo for 3 weeks. Placebo identical in appearance to naltrexone will be given twice daily to all patients assigned to placebo.
|
Naltrexone
n=6 participants at risk
In this arm, patients will receive active naltrexone for 3 weeks. 1 mg of naltrexone will be given twice daily to all patients assigned to active drug.
|
|---|---|---|
|
Nervous system disorders
Trouble sleeping
|
0.00%
0/6 • 3 weeks
|
33.3%
2/6 • Number of events 2 • 3 weeks
|
|
Nervous system disorders
Nightmares
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Psychiatric disorders
Irritable
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Psychiatric disorders
Hearing or seeing things
|
0.00%
0/6 • 3 weeks
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
|
Nervous system disorders
Numbness or tingling
|
0.00%
0/6 • 3 weeks
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
|
Gastrointestinal disorders
Dry mouth
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
|
Gastrointestinal disorders
Drooling or increased salivation
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle cramps or stiffness
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Nervous system disorders
Tremor or shakiness
|
0.00%
0/6 • 3 weeks
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
|
Nervous system disorders
Poor coordination or unsteadiness
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Trouble catching breath or hyperventilation
|
0.00%
0/6 • 3 weeks
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
|
Reproductive system and breast disorders
Menstrual irregularities
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Reproductive system and breast disorders
Loss of sexual interest
|
33.3%
2/6 • Number of events 2 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Reproductive system and breast disorders
Problems with sexual arousal
|
33.3%
2/6 • Number of events 2 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Reproductive system and breast disorders
Delayed or absent orgasm
|
33.3%
2/6 • Number of events 2 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Skin and subcutaneous tissue disorders
Sweating excessively
|
0.00%
0/6 • 3 weeks
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
|
Vascular disorders
Fluid retention or swelling
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
General disorders
Weight gain
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
0.00%
0/6 • 3 weeks
|
|
Nervous system disorders
Strange taste in mouth
|
0.00%
0/6 • 3 weeks
|
16.7%
1/6 • Number of events 1 • 3 weeks
|
Additional Information
David Mischoulon, MD, PhD, Director of Research
Depression Clinical and Research Program, Massachusetts General Hospital
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place