Trial Outcomes & Findings for N-acetylcysteine in the Treatment of PTSD and Addiction (NCT NCT02499029)
NCT ID: NCT02499029
Last Updated: 2018-08-29
Results Overview
Clinician Administered PTSD Scale IV (CAPS) The CAPS IV measures seventeen symptoms based on intensity and frequency. Intensity and frequency scores are summed to create a severity score for each question. Severity scores are summed to get a total score. A higher total score indicates a higher severity of PTSD symptoms.The full range for CAPS IV is 0-136.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
8 weeks
Results posted on
2018-08-29
Participant Flow
Participants were recruited from the VA medical center between March 2013 and April 2014.
Participant milestones
| Measure |
N-Acetylcysteine
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
17
|
|
Overall Study
COMPLETED
|
13
|
14
|
|
Overall Study
NOT COMPLETED
|
5
|
3
|
Reasons for withdrawal
| Measure |
N-Acetylcysteine
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
2
|
|
Overall Study
Physician Decision
|
2
|
1
|
|
Overall Study
Death
|
1
|
0
|
Baseline Characteristics
N-acetylcysteine in the Treatment of PTSD and Addiction
Baseline characteristics by cohort
| Measure |
N-Acetylcysteine
n=13 Participants
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
n=14 Participants
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
48.2 years
STANDARD_DEVIATION 8.6 • n=93 Participants
|
49.9 years
STANDARD_DEVIATION 8.1 • n=4 Participants
|
49.0 years
STANDARD_DEVIATION 8.2 • n=27 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
13 Participants
n=93 Participants
|
14 Participants
n=4 Participants
|
27 Participants
n=27 Participants
|
|
Substance Use Disorder (SUD)
Alcohol
|
10 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
Substance Use Disorder (SUD)
Cocaine
|
11 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Substance Use Disorder (SUD)
Opioid
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Post Traumatic Stress Disorder (PTSD)
CAPS IV
|
58.8 units on a scale
STANDARD_DEVIATION 21.2 • n=93 Participants
|
68.6 units on a scale
STANDARD_DEVIATION 23.7 • n=4 Participants
|
63.8 units on a scale
STANDARD_DEVIATION 22.6 • n=27 Participants
|
|
Post Traumatic Stress Disorder (PTSD)
PCL-M
|
45.7 units on a scale
STANDARD_DEVIATION 14.6 • n=93 Participants
|
43.4 units on a scale
STANDARD_DEVIATION 18.6 • n=4 Participants
|
44.5 units on a scale
STANDARD_DEVIATION 16.5 • n=27 Participants
|
PRIMARY outcome
Timeframe: 8 weeksClinician Administered PTSD Scale IV (CAPS) The CAPS IV measures seventeen symptoms based on intensity and frequency. Intensity and frequency scores are summed to create a severity score for each question. Severity scores are summed to get a total score. A higher total score indicates a higher severity of PTSD symptoms.The full range for CAPS IV is 0-136.
Outcome measures
| Measure |
N-Acetylcysteine
n=13 Participants
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
n=14 Participants
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
PTSD Symptoms
4 Weeks
|
38.7 units on a scale
Standard Deviation 20.0
|
52.8 units on a scale
Standard Deviation 36.9
|
|
PTSD Symptoms
8 Weeks
|
32.0 units on a scale
Standard Deviation 23.5
|
51.5 units on a scale
Standard Deviation 43.1
|
SECONDARY outcome
Timeframe: 8 weeksBeck Depression Inventory (BDI) The BDI measures presence and severity of depression. It has 21 questions that are rated from 0-3 with a highest possible score of 63. A higher score indicates a higher severity of depression.
Outcome measures
| Measure |
N-Acetylcysteine
n=13 Participants
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
n=14 Participants
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
Depression
Week 4
|
10.9 units on a scale
Standard Deviation 6.4
|
18.5 units on a scale
Standard Deviation 14.8
|
|
Depression
Week 8
|
9.9 units on a scale
Standard Deviation 6.7
|
19.3 units on a scale
Standard Deviation 15.8
|
SECONDARY outcome
Timeframe: 8 weeksVisual Analogue Scale (VAS) The VAS measures alcohol craving on a scale from 0 to 10. A higher score indicates a higher level of craving.
Outcome measures
| Measure |
N-Acetylcysteine
n=13 Participants
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
n=14 Participants
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
Craving
Intensity of Craving Week 4
|
1.8 units on a scale
Standard Deviation 2.1
|
2.9 units on a scale
Standard Deviation 2.8
|
|
Craving
Intensity of Craving Week 8
|
1.3 units on a scale
Standard Deviation 1.9
|
2.8 units on a scale
Standard Deviation 3.1
|
|
Craving
Amount of Craving Week 4
|
1.8 units on a scale
Standard Deviation 1.9
|
2.8 units on a scale
Standard Deviation 2.6
|
|
Craving
Amount of Craving Week 8
|
.7 units on a scale
Standard Deviation .7
|
2.8 units on a scale
Standard Deviation 2.8
|
|
Craving
Frequency of Craving Week 4
|
1.8 units on a scale
Standard Deviation 2.0
|
2.4 units on a scale
Standard Deviation 2.3
|
|
Craving
Frequency of Craving Week 8
|
1.0 units on a scale
Standard Deviation .9
|
3.0 units on a scale
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: 8 weeksPTSD Checklist - Military (PCL-M) The PCL-M is a seventeen question self-report, scored on a scale from 1 to 5, with possible scores ranging from 17 to 85. The scores from each question are summed to get a total score (17-85). A higher total indicates a higher severity of PTSD symptoms.
Outcome measures
| Measure |
N-Acetylcysteine
n=13 Participants
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
n=14 Participants
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
PTSD Symptoms
Week 4
|
33.8 units on a scale
Standard Deviation 10.6
|
41.9 units on a scale
Standard Deviation 21.7
|
|
PTSD Symptoms
Week 8
|
31.2 units on a scale
Standard Deviation 9.7
|
41.9 units on a scale
Standard Deviation 22.8
|
Adverse Events
N-Acetylcysteine
Serious events: 2 serious events
Other events: 12 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
N-Acetylcysteine
n=18 participants at risk
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
n=17 participants at risk
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
Cardiac disorders
Cardiac Arrhythmia
|
5.6%
1/18
|
0.00%
0/17
|
|
Blood and lymphatic system disorders
Syncopal Episode
|
0.00%
0/18
|
5.9%
1/17
|
|
Psychiatric disorders
Suicidality
|
0.00%
0/18
|
5.9%
1/17
|
|
Gastrointestinal disorders
Pancreatitis
|
5.6%
1/18
|
0.00%
0/17
|
|
Cardiac disorders
Death
|
5.6%
1/18
|
0.00%
0/17
|
Other adverse events
| Measure |
N-Acetylcysteine
n=18 participants at risk
Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
N-acetylcysteine: NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.
|
Placebo
n=17 participants at risk
Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).
Placebo: Identical looking placebo pills were administered each week.
|
|---|---|---|
|
General disorders
Dry Mouth
|
0.00%
0/18
|
11.8%
2/17
|
|
Gastrointestinal disorders
Abdominal Burning
|
5.6%
1/18
|
0.00%
0/17
|
|
Cardiac disorders
Palpitations
|
5.6%
1/18
|
0.00%
0/17
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
1/18
|
0.00%
0/17
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
16.7%
3/18
|
0.00%
0/17
|
|
General disorders
Dizziness
|
0.00%
0/18
|
5.9%
1/17
|
|
Infections and infestations
Fungal Rash
|
0.00%
0/18
|
5.9%
1/17
|
|
Gastrointestinal disorders
Heartburn
|
11.1%
2/18
|
0.00%
0/17
|
|
General disorders
Hot Flashes
|
5.6%
1/18
|
0.00%
0/17
|
|
Psychiatric disorders
Mood Changes
|
0.00%
0/18
|
5.9%
1/17
|
|
Infections and infestations
Poison Oak Rash
|
5.6%
1/18
|
0.00%
0/17
|
|
Respiratory, thoracic and mediastinal disorders
Shortness of Breath
|
0.00%
0/18
|
5.9%
1/17
|
|
Respiratory, thoracic and mediastinal disorders
Sinusitis
|
0.00%
0/18
|
5.9%
1/17
|
|
General disorders
Tingling Left Arm
|
0.00%
0/18
|
5.9%
1/17
|
|
Surgical and medical procedures
Tooth Extraction
|
0.00%
0/18
|
5.9%
1/17
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
|
11.1%
2/18
|
0.00%
0/17
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/18
|
5.9%
1/17
|
|
Infections and infestations
Spider Bite
|
5.6%
1/18
|
0.00%
0/17
|
|
Cardiac disorders
Unstable Cardiac Condition
|
5.6%
1/18
|
0.00%
0/17
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place