AlcoholismPhase 1/2NCT02966340
Repurposing alpha1 Noradrenergic Antagonists for Alcoholism Treatment
A Phase 1/2 study testing Prazosin in people with Alcoholism, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
Double-blind, placebo-controlled, cross-over design study examining the effects of a norepinephrine alpha1 receptor antagonist (prazosin) on stress reactivity in a laboratory stressor task. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcoholism
- What is being tested?
- Prazosin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2016to 12 Mar 2018
- Phase
- Phase 1/2
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Can read and write in English.
- Ages of 18-50 years.
- No current or lifetime history of Substance Use Disorder (except tobacco).
- Current Alcohol Use Disorder with 1-8 weeks completely free from alcohol consumption.
- Exclusion criteria are divided into three broad categories of Medical, Psychiatric/Behavioral, and Medications/Therapies.
Who cannot join
- Colorblind
- Blood alcohol concentration (BAC) > 0.00
- Systolic BP <100 after five minutes seated.
- Systolic BP drop >20 mmHg after two minutes standing.
- Systolic BP drop >10 mgHg AND report dizziness, lightheadedness, unsteadiness or other problems (e.g, nausea, blurry vision) after two minutes standing.
- Heart rate >100 beats/ minute after two minutes seated.
Show all 27Show fewer
- Heart rate <60 beats/ minute after two minutes seated.
- Scheduled for cataract surgery prior to study completion.
- Past or current coronary artery disease, cerebrovascular accident, congestive heart failure.
- Current renal insufficiency, liver insufficiency, pancreatitis, immunosuppressive therapy, or cancer with systemic effects or therapy.
- Benign positional vertigo, Meniere's disease or narcolepsy
- Current diabetes or polyneuropathy
- Previous allergic or adverse reaction to prazosin or other alpha1 norepinephrine antagonist.
- Other self-reported acute or unstable illness that, in the opinion of the study team, would preclude a safe and reliable study participation.
- Non-negative urine pregnancy test.
- Women of childbearing potential (see definition below) must agree to use one of the following forms of birth control until after study completion. Acceptable birth control is defined as the following methods of contraception: abstinence; hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy of partner and tubal ligation; "single" barrier methods of contraception (e.g. male condom, female condom, cervical cap, diaphragm, contraceptive sponge) with use of spermicide; or "double barrier" method of contraception (e.g. male condom with diaphragm, male condom with cervical cap).
- Breastfeeding
- NOTE: Women of childbearing potential are females who have experienced menarche and do not meet the criteria for women not of childbearing potential. Women not of childbearing potential are females who are permanently sterile (e.g., hysterectomy, bilateral oophorectomy) or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause.
- Self-reported lifetime diagnosis of schizophrenia, schizoaffective disorder, psychotic disorder not otherwise specified (NOS), bipolar disorder, borderline personality disorder, or any neurocognitive disorder.
- Currently prescribed or used within 72 hours: prazosin or other alpha1-NE antagonist (e.g., doxazosin, terazosin).
- Previous adequate trial of prazosin for alcohol use disorder or PTSD.
- Currently prescribed or used within 72 hours: Stimulants (e.g., d-amphetamine, methylphenidate) or alternative medications with stimulant properties (e.g., ephedra, pseudoephedrine).
- Currently prescribed or used within 72 hours: Sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra).
- Currently prescribed or used within 72 hours: beta-blockers (e.g., propranolol), alpha2 agonists (e.g., clonidine, guanfacine), or Serotonin-norepinephrine reuptake inhibitor (SNRI) anti-depressants (e.g., venlafaxine, duloxetine).
- Currently used daily or used within 72 hours: alpha1 agonists (e.g., midodrine, metaraminol, oxymetazoline, phenylephrine).
- Currently used daily or used within 72 hours: Benzodiazepines (e.g., diazepam, chlordiazepoxide, lorazepam, clonazepam, alprazolam), zolpidem (Ambien), zaleplon (Sonata), zopiclone (Imovane), eszopiclone (Lunesta), doxepin (Silenor).
- Currently prescribed and used daily or used within 72 hours: Trazodone (males only)
Trial locations and contacts
1 site in 1 country.
About this study
Double-blind, placebo-controlled, cross-over design study examining the effects of a norepinephrine alpha1 receptor antagonist (prazosin) on stress reactivity in a laboratory stressor task.
Read the detailed description
OBJECTIVES
The first objective of the current study is to examine norepinephrine alpha1 (NE-alpha1) receptor involvement in reactivity to unpredictable stressors in humans, by using the NPU stress task in conjunction with an alpha1-blocker, prazosin. The second objective of the study is to provide preliminary evidence that prazosin is effective at reducing stress-reactivity in alcoholics in early abstinence.
PARTICIPANTS
Sixty-four healthy adult participants and sixty-four participants with an Alcohol Use Disorder in early abstinence.
STUDY OVERVIEW
Sixty-four healthy adult participants (32 males \& 32 females) will be recruited to participate in a double-blind, placebo-controlled, cross-over design study examining the effects of a NE-alpha1 antagonist (prazosin) on the defensive (physiological and self-report affect) response to stressors using a well-validated animal-human translational stressor task. Participants will complete two overnight study visits where 2 mg prazosin and placebo are administered on separate visits separated by approximately 7 days. Drug order is randomly assigned and counterbalanced across participants (double-blind; study visits 1-2). On each of these two study visits, participants will complete the No Shock, Predictable Shock, Unpredictable Shock (NPU) task 90 minutes after drug administration. The NPU task is designed to examine stress reactivity to predictable and unpredictable stressors (i.e., electric shock). These two visits provide for a within-subject evaluation of the effect of acute antagonism of alpha1-NE receptors (via prazosin) to investigate the role of this NE mechanism in unpredictable (vs. predictable) stressor response.
After the full healthy adult/control sample has completed the study, the investigators will conduct preliminary data analysis to evaluate the first study hypothesis. These analyses are used to evaluate the sensitivity of the NPU task to NE-alpha1 mechanisms and its potential utility as an early surrogate endpoint for stress-related relapse mechanisms in alcoholism. The investigators will only recruit the sample of sixty-four alcoholic participants to complete the study if the first hypothesis is initially supported with healthy controls. These participants will meet Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for Alcohol Use Disorder (at least moderate severity) and be in early abstinence (1-8 weeks). All other study procedures will be identical for this sample.
OUTCOME MEASURES
The primary outcome is startle potentiation during the NPU task and the secondary outcome is self-reported retrospective fear/anxiety during the NPU task.
HYPOTHESES
- Prazosin (2mg vs. placebo) will reduce stress reactivity to unpredictable (vs. predictable) stressors measured via startle potentiation and self-report.
- Abstinent alcoholics (vs. controls) will display elevated stress reactivity to unpredictable (vs. predictable) stressors measured via startle potentiation and self-report.
- The predicted effects of prazosin on reducing stress reactivity to unpredictable (vs. predictable) stressors (Hypothesis 1) measured via startle potentiation and self-report will be moderated by alcoholism, such that the effects of prazosin will be larger in abstinent alcoholics than control participants.
- Conditions
- Alcoholism
- Being tested
- Prazosin, Placebo
- Keywords
- Alcoholism, Prazosin, Startle Potentiation, Norepinephrine, Anxiety, Fear, Stress
- Medical subject headings
- Alcoholism, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PrazosinDrug
2mg Prazosin
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Prazosin 1st visit, Placebo 2nd visit | Experimental | All participants receive 2mg prazosin and placebo in a cross-over design (e.g., one pill per visit). The order of prazosin vs placebo is counterbalanced between subjects (e.g., half participants receive prazosin at study visit 1 and half participants receive placebo at study visit 1). Receives: Drug: Prazosin; Drug: Placebo |
| Placebo 1st visit, Prazosin 2nd visit | Experimental | All participants receive 2mg prazosin and placebo in a cross-over design (e.g., one pill per visit). The order of prazosin vs placebo is counterbalanced between subjects (e.g., half participants receive prazosin at study visit 1 and half participants receive placebo at study visit 1). Receives: Drug: Prazosin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Startle Potentiation During Stress Reactivity Task.
The unpredictable shock and predictable shock startle response potentiation (vs. no shock) during the administration of the NPU stressor task. Values represent point estimate of effect from unadjusted general linear model analyses with 95% confidence intervals
Measured: 7 days
Secondary outcomes (1)
Self-reported Anxiety Potentiation During Stress Reactivity Task.
After the No-shock, Predictable-shock, Unpredictable-shock (NPU) task participants retrospectively reported their anxiety/fear during each condition on a 5-point likert scale (1 = 'Not at all anxious/ fearful', 5 = 'Very anxious/fearful'). The startle response is a defensive reflex that is elicited by an auditory stimuli (e.g., 50ms white noise) and measured via eyeblink electromyogram (EMG) activity over the obicularis oculi muscle. Startle potentiation is calculated as the increase in startle during unpredictable and predictable stressors relative to a no-stressor condition in the NPU task. Outcome is anxiety potentiation during unpredictable shock and predictable shock (vs. no-shock) conditions. This was assessed with a single question, total possible range was 1-5.
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2016 (estimated)
- Study start1 Nov 2016
- Primary completion12 Mar 2018
- Study completion12 Mar 2018
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.
- Other trials for AlcoholismStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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 1/2
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- John J Curtin, PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02966340
- Sponsor's protocol ID
- 2014-0966
- Other IDs
- F31AA022845-01, Kaye2
- Status last verified
- May 2019
- First submitted
- 15 Nov 2016
- Last updated
- 28 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators will share on Open Science Framework de-identified and anonymous physiology (e.g., Electromyography (EMG) startle response) and self-report survey/questionnaire data collected from participants during the study.
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repurposing alpha1 Noradrenergic Antagonists for Alcoholism Treatment
- ClinicalTrials.gov ID
- NCT02966340
- Acronym / sponsor ID
- 2014-0966
- Conditions
- Alcoholism
- Keywords
- Alcoholism, Prazosin, Startle Potentiation, Norepinephrine, Anxiety, Fear, Stress
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 12 Mar 2018 (actual)
- Study completion
- 12 Mar 2018 (actual)
- First posted
- 17 Nov 2016 (estimated)
- Results
- Posted 28 May 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Double-blind, placebo-controlled, cross-over design study examining the effects of a norepinephrine alpha1 receptor antagonist (prazosin) on stress reactivity in a laboratory stressor task.
Detailed description
OBJECTIVES
The first objective of the current study is to examine norepinephrine alpha1 (NE-alpha1) receptor involvement in reactivity to unpredictable stressors in humans, by using the NPU stress task in conjunction with an alpha1-blocker, prazosin. The second objective of the study is to provide preliminary evidence that prazosin is effective at reducing stress-reactivity in alcoholics in early abstinence.
PARTICIPANTS
Sixty-four healthy adult participants and sixty-four participants with an Alcohol Use Disorder in early abstinence.
STUDY OVERVIEW
Sixty-four healthy adult participants (32 males \& 32 females) will be recruited to participate in a double-blind, placebo-controlled, cross-over design study examining the effects of a NE-alpha1 antagonist (prazosin) on the defensive (physiological and self-report affect) response to stressors using a well-validated animal-human translational stressor task. Participants will complete two overnight study visits where 2 mg prazosin and placebo are administered on separate visits separated by approximately 7 days. Drug order is randomly assigned and counterbalanced across participants (double-blind; study visits 1-2). On each of these two study visits, participants will complete the No Shock, Predictable Shock, Unpredictable Shock (NPU) task 90 minutes after drug administration. The NPU task is designed to examine stress reactivity to predictable and unpredictable stressors (i.e., electric shock). These two visits provide for a within-subject evaluation of the effect of acute antagonism of alpha1-NE receptors (via prazosin) to investigate the role of this NE mechanism in unpredictable (vs. predictable) stressor response.
After the full healthy adult/control sample has completed the study, the investigators will conduct preliminary data analysis to evaluate the first study hypothesis. These analyses are used to evaluate the sensitivity of the NPU task to NE-alpha1 mechanisms and its potential utility as an early surrogate endpoint for stress-related relapse mechanisms in alcoholism. The investigators will only recruit the sample of sixty-four alcoholic participants to complete the study if the first hypothesis is initially supported with healthy controls. These participants will meet Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for Alcohol Use Disorder (at least moderate severity) and be in early abstinence (1-8 weeks). All other study procedures will be identical for this sample.
OUTCOME MEASURES
The primary outcome is startle potentiation during the NPU task and the secondary outcome is self-reported retrospective fear/anxiety during the NPU task.
HYPOTHESES
- Prazosin (2mg vs. placebo) will reduce stress reactivity to unpredictable (vs. predictable) stressors measured via startle potentiation and self-report.
- Abstinent alcoholics (vs. controls) will display elevated stress reactivity to unpredictable (vs. predictable) stressors measured via startle potentiation and self-report.
- The predicted effects of prazosin on reducing stress reactivity to unpredictable (vs. predictable) stressors (Hypothesis 1) measured via startle potentiation and self-report will be moderated by alcoholism, such that the effects of prazosin will be larger in abstinent alcoholics than control participants.
Study design
- Primary purpose
- Screening
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prazosin 1st visit, Placebo 2nd visit | Experimental | Drug: Prazosin, Drug: PlaceboAll participants receive 2mg prazosin and placebo in a cross-over design (e.g., one pill per visit). The order of prazosin vs placebo is counterbalanced between subjects (e.g., half participants receive prazosin at study visit 1 and half participants receive placebo at study visit 1). |
| Placebo 1st visit, Prazosin 2nd visit | Experimental | Drug: Prazosin, Drug: PlaceboAll participants receive 2mg prazosin and placebo in a cross-over design (e.g., one pill per visit). The order of prazosin vs placebo is counterbalanced between subjects (e.g., half participants receive prazosin at study visit 1 and half participants receive placebo at study visit 1). |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Can read and write in English.
- Ages of 18-50 years.
- No current or lifetime history of Substance Use Disorder (except tobacco).
- Current Alcohol Use Disorder with 1-8 weeks completely free from alcohol consumption.
- Exclusion criteria are divided into three broad categories of Medical, Psychiatric/Behavioral, and Medications/Therapies.
Key exclusion criteria (27 listed)
- Colorblind
- Blood alcohol concentration (BAC) > 0.00
- Systolic BP <100 after five minutes seated.
- Systolic BP drop >20 mmHg after two minutes standing.
- Systolic BP drop >10 mgHg AND report dizziness, lightheadedness, unsteadiness or other problems (e.g, nausea, blurry vision) after two minutes standing.
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 |
|---|---|---|
| Prazosin2mg Prazosin | Drug | Placebo 1st visit, Prazosin 2nd visit, Prazosin 1st visit, Placebo 2nd visit |
| PlaceboPlacebo | Drug | Placebo 1st visit, Prazosin 2nd visit, Prazosin 1st visit, Placebo 2nd visit |
Primary outcome
Startle Potentiation During Stress Reactivity Task.
Time frame: 7 days
The unpredictable shock and predictable shock startle response potentiation (vs. no shock) during the administration of the NPU stressor task. Values represent point estimate of effect from unadjusted general linear model analyses with 95% confidence intervals
1 secondary outcome
Self-reported Anxiety Potentiation During Stress Reactivity Task.
Time frame: 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Dr. John Curtin's Addiction Research CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The investigators will share on Open Science Framework de-identified and anonymous physiology (e.g., Electromyography (EMG) startle response) and self-report survey/questionnaire data collected from participants during the study.
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.
John J Curtin, PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Prazosin in people with Alcoholism, run by University of Wisconsin, Madison 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 27 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 28 May 2019. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 28 May 2019). 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?
Startle Potentiation During Stress Reactivity Task. (time frame: 7 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 May 2019.