AlcoholismPhase 3NCT00338962

Naltrexone & SSRI in Alcoholics With Depression/PTSD

A Phase 3 study testing paroxetine, desipramine and Naltrexone in people with Alcoholism and Depression, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The purpose of this study is to evaluate the efficacy of naltrexone in combination with an SSRI to reduce alcohol consumption in alcoholic patients with comorbid PTSD and depression. Read more about this study

Who is it for?: Ages 21 to 75 years
Conditions the study is for: Alcoholism, Depression, PTSD
What is being tested?: paroxetine, desipramine and Naltrexone
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 88 participants
Where: 1 siteUnited States
Study dates: Oct 2001to Jul 2015
Phase: Phase 3
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 21 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

DSM-IV diagnosis of alcohol dependence and current DSM-IV depressive disorder or PTSD
a recent episode of heavy drinking
outpatient, sober from alcohol and other abused substance for at least 2 days before randomization
stable medication regiment for at least 2 weeks
women on adequate methods of contraception

Who cannot join

current opioid dependence or abuse
history (within the last 3 months) of opioid dependence or abuse
pregnant
history of psychotic disorders or current treatment with antipsychotic medications
medication thought to influence drinking including: acamprosate, disulfiram, naltrexone, ondansetron, valproic acid or tegretol
current (within the lst 6 months) use of MAO inhibitors

Show all 9Show fewer

suicidal active ideation or intent
significant underlying medical condition
history of cardiac condition abnormalities

Trial locations and contacts

1 site in 1 country.

United States1 site

VA Connecticut Healthcare Systems
West Haven, Connecticut, 06516

Other trials in United States

About this study

The purpose of this study is to evaluate the efficacy of naltrexone in combination with an SSRI to reduce alcohol consumption in alcoholic patients with comorbid PTSD and depression.

We hypothesize that the combination of naltrexone and SSRI will exhibit a greater decrease in alcohol consumption than that seen with treatment with SSRI alone, or with a combination of another class of antidepressant and naltrexone. We also hypothesize that SSRI will be effective in treating PTSD and depressive symptoms and naltrexone will be well tolerated.

Read the detailed description

OBJECTIVE: Alcoholics with current comorbid mental disorders constitute the majority of alcoholics in clinical settings. Although there are two FDA approved medications for the treatment of alcoholism (naltrexone and disulfiram), there are no established pharmacotherapies for individuals with comorbid alcoholism and psychiatric illnesses. Studies suggest that the class of antidepressants known as serotonin selective reuptake inhibitors (SSRIs) is effective in reducing alcohol use in depressed individuals. In addition, a small open label study has shown that SSRIs have similar effects on individuals with comorbid PTSD and alcoholism. Preclinical studies have shown that the combination of a serotonergic agent and naltrexone was more effective than either medication alone in suppressing alcohol intake. To address this issue, we are conducting a 13 week randomized clinical trial evaluating the effects of paroxetine, desipramine and naltrexone in reducing alcohol use in alcohol dependent individuals who currently meet DSM-IV diagnosis for Depressive Disorder or PTSD. RESEARCH PLAN: One hundred and twenty subjects who are alcohol dependent patients with comorbid PTSD or Depressive Disorder will be recruited from the following West Haven VA sources: the Substance Abuse Treatment program, the PTSD clinic, the Women's clinic, clinical referrals and advertisement. These subjects will be randomized in a double-blind fashion to one of four cells. We will compare paroxetine versus desipramine and naltrexone versus placebo. The antidepressant will be started at a low dose and titrated upward on a fixed schedule. The target dose will be 40mg for paroxetine and 200mg for desipramine. Minimum dosage permitted for study retention will be 20mg for paroxetine and 150mg for desipramine. Pharmacological treatments will last 13 weeks. Psychosocial treatment will involve medication compliance therapy, using the Microelectric Event Monitoring (MEMS) bottle caps. The specific aim of the research is to compare the relative effectiveness of paroxetine versus desipramine and naltrexone versus placebo in reducing the quantity and frequency of alcohol consumption. METHODOLOGY: The primary outcome measures of major interest will include: frequency and quantity of alcohol consumption, self-reported craving, self-reported psychiatric and emotional distress, diagnostic assessment or psychiatric symptoms and side effects. These outcomes will be measured by the following: self-assessments, Timeline Followback, Hamilton Depression and anxiety scales, CAPS, ASI, Quality of Life, breathalyzer tests and monthly liver function tests.

Conditions: Alcoholism, Depression, PTSD
Being tested: paroxetine, desipramine, Naltrexone, Placebo
Keywords: SSRI, treatment, naltrexone, alcohol dependence, Desipramine, depression, PTSD
Medical subject headings: Alcoholism, Depression, Stress Disorders, Post-Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

paroxetineDrug
Also called paxil
paroxetine (40mg/day)
desipramineDrug
Also called Norpramin
200 mg per day
NaltrexoneDrug
Also called Vivitrol
50 mg per day
PlaceboDrug
placebo

Study groups in NCT00338962
Study group	Role	What they receive
Paroxetine and naltrexone	Active comparator	Paroxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment. Receives: Drug: paroxetine; Drug: Naltrexone
paroxetine and placebo	Active comparator	Paroxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day. Receives: Drug: paroxetine; Drug: Placebo
Desipramine and naltrexone	Active comparator	Desipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment. Receives: Drug: desipramine; Drug: Naltrexone
Desipramine and placebo	Active comparator	Desipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day. Receives: Drug: desipramine; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)
The OCDS is a 14-item (rated 0-4), self-administered questionnaire for characterizing and quantifying the obsessive and compulsive cognitive aspects of craving and heavy (alcoholic) drinking, such as drinking-related thought, urges to drink, and the ability to resist those thoughts and urges. A higher total score indicates higher craving and ranges from 0-48.
Measured: beginning of treatment (week 1), and end of treatment (13 weeks)
Clinician-Administered PTSD Scale (CAPS)
The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to:
Make current (past month) diagnosis of PTSD Make lifetime diagnosis of PTSD Assess PTSD symptoms over the past week Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD >80=Extreme PTSD
Measured: beginning of treatment (week 1), and end of treatment (13 weeks)
Hamilton Depression Rating Scale (HAM-D)
The HAM-D ranges from 0 (Normal) to >23 (Very Severe Depression)
Measured: beginning of treatment (week 1), and end of treatment (13 weeks)
Mean Number of Side Effects
Differences in mean number of side effects reported for each group. Side effects and common adverse symptoms were evaluated by the research staff weekly, using a modified version of the ystematic Assessment for Treatment Emergent Events. The symptoms that are known to be associated with treatment with desipramine, paroxetine, and naltrexone were specifically screened or on a weekly basis. The symptoms were then clustered into the following categories: gastrointestinal, emotional, cold and flu symptoms, skin, sexual, neurological, and cardiac.
Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2001Jul 2015

First posted20 Jun 2006 (estimated)
Study startOct 2001
Primary completionJul 2015
Study completionJul 2015

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 AlcoholismStudies of the same condition, open and under way.
More trials run by Yale UniversityThe 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 88 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00338962
Sponsor's protocol ID: HIC # 11637
Status last verified: Jan 2016
First submitted: 15 Jun 2006
Last updated: 5 Feb 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology. 2012 Mar;37(4):996-1004. doi: 10.1038/npp.2011.283. Epub 2011 Nov 16.
PubMed 22089316

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingPhase 1
Environment and Alcohol: A Pilot Study
Alcohol Use Disorder
RecruitingObservational study
SMART-r: Substance Monitoring and Active Relapse Tracking Repository
Alcoholism, Substance-Related Disorders
Not yet recruiting
A MRT to Optimize a JITAI for Alcohol Craving and Suicide Ideation
Alcohol Use Disorder (AUD), Suicide Ideation
RecruitingPhase 2
Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder
Alcohol Use Disorder

All Alcoholism trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Naltrexone & SSRI in Alcoholics With Depression/PTSD
ClinicalTrials.gov ID: NCT00338962
Acronym / sponsor ID: HIC # 11637
Conditions: Alcoholism, Depression, PTSD
Keywords: SSRI, treatment, naltrexone, alcohol dependence, Desipramine, depression, PTSD
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 88 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Study start: Oct 2001
Primary completion: Jul 2015 (actual)
Study completion: Jul 2015 (actual)
First posted: 20 Jun 2006 (estimated)
Results: Posted 5 Feb 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the efficacy of naltrexone in combination with an SSRI to reduce alcohol consumption in alcoholic patients with comorbid PTSD and depression.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
Paroxetine and naltrexone	Active comparator	Drug: paroxetine, Drug: NaltrexoneParoxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment.
paroxetine and placebo	Active comparator	Drug: paroxetine, Drug: PlaceboParoxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day.
Desipramine and naltrexone	Active comparator	Drug: desipramine, Drug: NaltrexoneDesipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment.
Desipramine and placebo	Active comparator	Drug: desipramine, Drug: PlaceboDesipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day.

Who may qualify

Ages: 21 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

DSM-IV diagnosis of alcohol dependence and current DSM-IV depressive disorder or PTSD
a recent episode of heavy drinking
outpatient, sober from alcohol and other abused substance for at least 2 days before randomization
stable medication regiment for at least 2 weeks
women on adequate methods of contraception

Key exclusion criteria (9 listed)

current opioid dependence or abuse
history (within the last 3 months) of opioid dependence or abuse
pregnant
history of psychotic disorders or current treatment with antipsychotic medications
medication thought to influence drinking including: acamprosate, disulfiram, naltrexone, ondansetron, valproic acid or tegretol

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
paroxetineAlso: paxilparoxetine (40mg/day)	Drug	Paroxetine and naltrexone, paroxetine and placebo
desipramineAlso: Norpramin200 mg per day	Drug	Desipramine and naltrexone, Desipramine and placebo
NaltrexoneAlso: Vivitrol50 mg per day	Drug	Desipramine and naltrexone, Paroxetine and naltrexone
Placeboplacebo	Drug	Desipramine and placebo, paroxetine and placebo

Primary outcome

Mean Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)
Time frame: beginning of treatment (week 1), and end of treatment (13 weeks)
The OCDS is a 14-item (rated 0-4), self-administered questionnaire for characterizing and quantifying the obsessive and compulsive cognitive aspects of craving and heavy (alcoholic) drinking, such as drinking-related thought, urges to drink, and the ability to resist those thoughts and urges. A higher total score indicates higher craving and ranges from 0-48.
Clinician-Administered PTSD Scale (CAPS)
Time frame: beginning of treatment (week 1), and end of treatment (13 weeks)
The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to: Make current (past month) diagnosis of PTSD Make lifetime diagnosis of PTSD Assess PTSD symptoms over the past week Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD >80=Extreme PTSD
Hamilton Depression Rating Scale (HAM-D)
Time frame: beginning of treatment (week 1), and end of treatment (13 weeks)
The HAM-D ranges from 0 (Normal) to >23 (Very Severe Depression)
Mean Number of Side Effects
Time frame: 12 weeks
Differences in mean number of side effects reported for each group. Side effects and common adverse symptoms were evaluated by the research staff weekly, using a modified version of the ystematic Assessment for Treatment Emergent Events. The symptoms that are known to be associated with treatment with desipramine, paroxetine, and naltrexone were specifically screened or on a weekly basis. The symptoms were then clustered into the following categories: gastrointestinal, emotional, cold and flu symptoms, skin, sexual, neurological, and cardiac.

Results and safety

Results posted to the registry on 5 Feb 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Paroxetine and Naltrexone	22	14
Paroxetine and Placebo	20	16
Desipramine and Naltrexone	22	16
Desipramine and Placebo	24	21

Primary outcome: Mean Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)

Time frame: beginning of treatment (week 1), and end of treatment (13 weeks). Mean (Standard Error). Unit: units on a scale

Measure	Paroxetine and Naltrexone n = 14	Paroxetine and Placebo n = 16	Desipramine and Naltrexone n = 16	Desipramine and Placebo n = 21
Week 1	21.273 (2.547)	20.700 (2.672)	18.500 (2.547)	21.458 (2.439)
Week 13	10.013 (3.009)	9.690 (3.025)	4.296 (2.847)	7.489 (2.483)

Primary outcome: Clinician-Administered PTSD Scale (CAPS)

Time frame: beginning of treatment (week 1), and end of treatment (13 weeks). Mean (Standard Error). Unit: units on a scale

Measure	Paroxetine and Naltrexone n = 14	Paroxetine and Placebo n = 16	Desipramine and Naltrexone n = 16	Desipramine and Placebo n = 21
Beginning of Treatment	73.54 (5.007)	69.810 (5.166)	62.500 (5.047)	77.833 (4.832)
End of Treatment	40.024 (5.53)	36.591 (5.570)	26.751 (5.353)	41.392 (4.949)

Paroxetine and Naltrexone vs Paroxetine and Placebo vs Desipramine and Naltrexone vs Desipramine and Placebo: p = 0.00, Mixed Models Analysis

Primary outcome: Hamilton Depression Rating Scale (HAM-D)

Time frame: beginning of treatment (week 1), and end of treatment (13 weeks). Mean (Standard Error). Unit: units on a scale

Measure	Paroxetine and Naltrexone n = 14	Paroxetine and Placebo n = 16	Desipramine and Naltrexone n = 16	Desipramine and Placebo n = 21
Beginning of Treatment	13.273 (1.112)	10.950 (1.167)	11.195 (1.132)	13.167 (1.065)
End of Treatment	9.328 (1.256)	8.238 (1.299)	8.563 (1.201)	8.943 (1.117)

Primary outcome: Mean Number of Side Effects

Time frame: 12 weeks. Mean (Standard Error). Unit: side effects

Measure	Paroxetine and Naltrexone n = 22	Paroxetine and Placebo n = 20	Desipramine and Naltrexone n = 22	Desipramine and Placebo n = 24
Gastrointestinal symptoms	3.651 (.487)	2.688 (.513)	3.052 (.475)	3.653 (.431)
Emotional Symptoms	4.874 (.686)	3.963 (.719)	3.727 (.689)	5.248 (.629)
Neurological Symptoms	6.212 (1.058)	5.078 (1.106)	4.201 (1.047)	4.566 (.970)
Cold Symptoms	2.182 (.490)	2.393 (.512)	1.891 (.483)	2.253 (.447)
Skin Symptoms	1.002 (.240)	.859 (.252)	.591 (.236)	1.057 (.215)
Sexual Symptoms	.877 (.241)	.932 (.252)	.737 (.238)	.736 (.219)
Cardiac Symptoms	.416 (.093)	.474 (.101)	.389 (.089)	.356 (.076)

Paroxetine and Naltrexone vs Paroxetine and Placebo vs Desipramine and Naltrexone vs Desipramine and Placebo: p = 0.007, ANOVA

Adverse events

Time frame: 9 weeks afters study medication. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Paroxetine and Naltrexone	1 of 22 (4.5%)	1 of 22 (4.5%)	Not reported
Paroxetine and Placebo	2 of 20 (10%)	1 of 20 (5%)	Not reported
Desipramine and Naltrexone	0 of 22 (0%)	2 of 22 (9.1%)	Not reported
Desipramine and Placebo	0 of 24 (0%)	2 of 24 (8.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22089316Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology. 2012 Mar;37(4):996-1004. doi: 10.1038/npp.2011.283. Epub 2011 Nov 16.
Published paperLink provided by the sponsor.

Related trials for Alcoholism

Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingPhase 1
Environment and Alcohol: A Pilot Study
Alcohol Use Disorder
RecruitingObservational study
SMART-r: Substance Monitoring and Active Relapse Tracking Repository
Alcoholism, Substance-Related Disorders
Not yet recruiting
A MRT to Optimize a JITAI for Alcohol Craving and Suicide Ideation
Alcohol Use Disorder (AUD), Suicide Ideation
RecruitingPhase 2
Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder
Alcohol Use Disorder

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.

Ismene Petrakis, M.D. principal investigator

Yale University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing paroxetine, desipramine and Naltrexone in people with Alcoholism and Depression, run by Yale University at 1 site in United States.

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 5 inclusion and 9 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 5 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 5 Feb 2016). 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?

Mean Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS) (time frame: beginning of treatment (week 1), and end of treatment (13 weeks)). The study lists 4 primary outcomes in all. 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 NCT00338962, 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 5 Feb 2016.