PTSDPhase 2NACNCT02499029
N-acetylcysteine in the Treatment of PTSD and Addiction
A Phase 2 study testing N-acetylcysteine in people with PTSD and Addiction, run by Medical University of South Carolina.
Trial summary
Examine the effects of N-acetylcysteine on PTSD symptoms, craving and substance use in veterans with PTSD and comorbid substance use disorders. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- No sites listed yet
- Study dates
- Feb 2013to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-65 year old
- U.S. military Veteran, Reservist, or National Guard member
- DSM-IV diagnostic criteria for current (past 6 months) SUD and PTSD or subthreshold PTSD (i.e., met criteria for cluster B (re-experiencing) and either cluster C (avoidance) or D (hyperarousal), as well as duration of one month and clinically significant impairment)
- Score of > 21 on the Mini-Mental State Exam (MMSE).
Who cannot join
- Unstable medical conditions
- Bipolar or psychotic disorders
- Seizures or asthma
- Prior treatment with NAC
- Suicidality
- Enrolled in ongoing PTSD treatment (pharmacotherapy or psychosocial)
- Females: could not be pregnant or lactating
About this study
Official title: Glial Regulators for Treating Comorbid Posttraumatic Stress and Substance Abuse Disorders
Examine the effects of N-acetylcysteine on PTSD symptoms, craving and substance use in veterans with PTSD and comorbid substance use disorders.
Read the detailed description
With the increased number of military veterans returning from conflicts in Afghanistan and Iraq diagnosed with posttraumatic stress disorder (PTSD), there is a high vulnerability of these individuals to develop a substance use disorder (SUD). While there have been a host of studies focused largely on dopaminergic mechanisms of drug reward, they have not led to the development of adequate treatments for either preventing people diagnosed with PTSD from developing SUD or for treating comorbid PTSD/SUD. Based on extensive work with addictive drugs and preliminary data from our group, the investigators propose that stress impairs prefrontal cortex regulation of the basal ganglia habit circuitry and this pathology renders PTSD patients susceptible to developing SUD. Moreover, the known effects of addictive drugs to further impair prefrontal regulation are synergistic with this pathology, thereby making treatment of comorbid PTSD/SUD particularly difficult. Preclinical studies have revealed that glutamate levels within the nucleus accumbens have been implicated in drug seeking behavior in the animal model of relapse. The amino acid precursor N-acetylcysteine (NAC) appears to restore glutamate to normal levels and may also prevent glutamate levels from spiking following subsequent stimulant use. The primary goal of the proposed study is to evaluate the efficacy and safety of N-acetylcysteine in preventing relapse in drug dependent individuals with PTSD or subthreshold PTSD. Veterans with substance use disorders who have achieved at lease one week of abstinence will be randomized to either placebo or NAC (2400-3600mg/day) for 8 weeks.
- Being tested
- N-acetylcysteine, Placebo
- Medical subject headings
- Stress Disorders, Post-Traumatic, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called NAC
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.
PlaceboDrug
Identical looking placebo pills were administered each week.
| Study group | Role | What they receive |
|---|---|---|
| N-Acetylcysteine | Experimental | 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. Receives: Drug: N-acetylcysteine |
| Placebo | Placebo comparator | 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PTSD Symptoms
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.
Measured: 8 weeks
Secondary outcomes (3)
Depression
Beck 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.
Measured: 8 weeks
Craving
Visual Analogue Scale (VAS) The VAS measures alcohol craving on a scale from 0 to 10. A higher score indicates a higher level of craving.
Measured: 8 weeks
PTSD Symptoms
PTSD 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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2015 (estimated)
- Study startFeb 2013
- Primary completionSep 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PTSDStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02499029
- Sponsor's protocol ID
- Pro00021986
- Acronym
- NAC
- Status last verified
- Jul 2018
- First submitted
- 1 Jul 2015
- Last updated
- 29 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Back SE, McCauley JL, Korte KJ, Gros DF, Leavitt V, Gray KM, Hamner MB, DeSantis SM, Malcolm R, Brady KT, Kalivas PW. A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders. J Clin Psychiatry. 2016 Nov;77(11):e1439-e1446. doi: 10.4088/JCP.15m10239.
PubMed 27736051
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glial Regulators for Treating Comorbid Posttraumatic Stress and Substance Abuse Disorders
- ClinicalTrials.gov ID
- NCT02499029
- Acronym / sponsor ID
- NAC / Pro00021986
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 15 Jul 2015 (estimated)
- Results
- Posted 29 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Examine the effects of N-acetylcysteine on PTSD symptoms, craving and substance use in veterans with PTSD and comorbid substance use disorders.
Detailed description
With the increased number of military veterans returning from conflicts in Afghanistan and Iraq diagnosed with posttraumatic stress disorder (PTSD), there is a high vulnerability of these individuals to develop a substance use disorder (SUD). While there have been a host of studies focused largely on dopaminergic mechanisms of drug reward, they have not led to the development of adequate treatments for either preventing people diagnosed with PTSD from developing SUD or for treating comorbid PTSD/SUD. Based on extensive work with addictive drugs and preliminary data from our group, the investigators propose that stress impairs prefrontal cortex regulation of the basal ganglia habit circuitry and this pathology renders PTSD patients susceptible to developing SUD. Moreover, the known effects of addictive drugs to further impair prefrontal regulation are synergistic with this pathology, thereby making treatment of comorbid PTSD/SUD particularly difficult. Preclinical studies have revealed that glutamate levels within the nucleus accumbens have been implicated in drug seeking behavior in the animal model of relapse. The amino acid precursor N-acetylcysteine (NAC) appears to restore glutamate to normal levels and may also prevent glutamate levels from spiking following subsequent stimulant use. The primary goal of the proposed study is to evaluate the efficacy and safety of N-acetylcysteine in preventing relapse in drug dependent individuals with PTSD or subthreshold PTSD. Veterans with substance use disorders who have achieved at lease one week of abstinence will be randomized to either placebo or NAC (2400-3600mg/day) for 8 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N-Acetylcysteine | Experimental | Drug: N-acetylcysteineEligible 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. |
| Placebo | Placebo comparator | Drug: PlaceboIdentical 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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18-65 year old
- U.S. military Veteran, Reservist, or National Guard member
- DSM-IV diagnostic criteria for current (past 6 months) SUD and PTSD or subthreshold PTSD (i.e., met criteria for cluster B (re-experiencing) and either cluster C (avoidance) or D (hyperarousal), as well as duration of one month and clinically significant impairment)
- Score of > 21 on the Mini-Mental State Exam (MMSE).
Key exclusion criteria (7 listed)
- Unstable medical conditions
- Bipolar or psychotic disorders
- Seizures or asthma
- Prior treatment with NAC
- Suicidality
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: NACNAC 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. | Drug | N-Acetylcysteine |
| PlaceboIdentical looking placebo pills were administered each week. | Drug | Placebo |
Primary outcome
PTSD Symptoms
Time frame: 8 weeks
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.
3 secondary outcomes
Depression
Time frame: 8 weeks
Craving
Time frame: 8 weeks
PTSD Symptoms
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27736051Back SE, McCauley JL, Korte KJ, Gros DF, Leavitt V, Gray KM, Hamner MB, DeSantis SM, Malcolm R, Brady KT, Kalivas PW. A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders. J Clin Psychiatry. 2016 Nov;77(11):e1439-e1446. doi: 10.4088/JCP.15m10239.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing N-acetylcysteine in people with PTSD and Addiction, run by Medical University of South Carolina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PTSD Symptoms (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02499029, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2018.