Alcohol-Related DisordersPhase 2NCT01227980
Corticotropin-Releasing Hormone Receptor 1 (CRH1) Antagonism in Anxious Alcoholics^
A Phase 2 study testing Pexacerfont in people with Alcohol-Related Disorders and Alcohol Dependence, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial summary
Background: Individuals who are dependent on alcohol often have feelings of anxiety, irritability, anger, and depression. These feelings, as well as stress, may contribute to the risk of relapse and continued drinking. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Alcohol-Related Disorders, Alcohol Dependence, Alcoholism
- What is being tested?
- Pexacerfont
- 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
- Oct 2010to Jul 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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed written informed consent:
- Patients must be competent to understand the nature of the study, sign the informed consent prior to any study-related procedures, agree to comply with the prescribed dosage regimens, agree to remain hospitalized at the NIH Clinical Center throughout the duration of the study and to return for follow-up visits as specified, and agree to communicate to study personnel about adverse events and concomitant medication use.
- Target population:
- DSM-IV diagnosis of alcohol dependence on SCID interview,
- alcohol problems as primary complaint among substance use disorders,
- alcohol use within the last month.
Show all 12Show fewer
- Spielberger trait anxiety inventory score > 39.
- Right-handedness
- Age and sex:
- Men and women, ages 21 65 years.
- Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) prior to enrollment, and agree to using an adequate method of contraception to avoid pregnancy for a period of 6 months beginning from first dose of randomized treatment. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Adequate methods of contraception are practicing complete abstinence from intercourse for two weeks prior to administration of study drug; having a male sexual partner(s) who is surgically sterilized (vasectomy with documentation of azoospermia) prior to inclusion; having a sexual partner(s) who is/are exclusively female; using oral contraceptives (either combined or progestogen only) with single-barrier method of contraception consisting of spermicide and condom or diaphragm; using double-barrier contraception, specifically, a condom plus spermicide and a female diaphragm or cervical cap; using an approved intrauterine device (IUD) with established efficacy.
- Men, unless surgically sterilized (vasectomy with documentation of azoospermia), must agree to practicing abstinence or using barrier contraception, and not donate sperm, for a period of 6 months beginning from first dose of randomized treatment.
Who cannot join
- General:
- Investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
- Employees of Bristol-Meyers Squibb (BMS) or immediate family of BMS employees.
- Subjects with current participation in another clinical study in which the subject is or will be exposed to an investigational or non investigational drug or device; participation in a clinical study for an illness unrelated to alcohol use within the preceding month; or any previous participation in a trial involving pexacerfont or closely related compounds.
- Inability or unwillingness to participate in an MR scan, including presence of ferromagnetic metallic objects in the body, or pronounced claustrophobia
- Any medical or psychiatric condition or laboratory finding that, in the judgment of the investigator could adversely affect subject safety or study integrity.
Show all 46Show fewer
- Subjects who are unlikely or unable to complete this study because of impending or likely incarceration while on the protocol.
- Subjects who are required to receive treatment by a court of law or involuntarily committed to treatment.
- Sex and reproductive status:
- Inability or unwillingness to practice contraception as described above
- Women who are pregnant, breastfeeding, or planning to become pregnant within 6 months from the administration of first study drug dose.
- Men who are planning to father a child within 6 months from the
- administration of the first study drug dose
- Exclusionary psychiatric conditions:
- Past or present diagnosis of schizophrenia, bipolar disease, or any psychotic disorder other than one determined to be substance induced; past or present diagnosis of dementia, or any other disorder which has led to a clinically significant cognitive impairment; any other psychiatric condition which at the present time requires, or in the past month has required pharmacological intervention other than standard withdrawal treatment as described in the NIAAA Assessment and Treatment Protocol (#05-AA-0121).
- A personality disorder which, in the investigator s judgment could lead to non-compliance with study procedures.
- Subjects, who in the investigator's judgment, pose a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) in the last 2 months.
- Positive urine test for illegal drug use.
- Exclusionary medical history and concurrent medical conditions:
- Subjects with clinically significant thyroid pathology that would interfere with efficacy or safety evaluations, or who are undergoing treatment for their thyroid pathology (e.g., thyroid supplementation).
- Subjects with adrenal or pituitary pathology as evidenced by medical history or suggested from abnormal screening laboratory tests.
- Subjects with a significant history (as judged by the Investigator) of seizure disorder (e.g., epilepsy or withdrawal seizures), other significant neurological disorders (e.g., Parkinson s Disease, multiple sclerosis, stroke, neurodegenerative disease, cerebral palsy) or severe head trauma.
- Subjects with active liver disease or a history of hepatic intolerance to medications that in the Investigator s judgment, is medically significant.
- Subjects with a history of Diabetes Mellitus Type I and II or gastric bypass or reduction surgery.
- Subjects with Human Immunodeficiency Virus (HIV) infection.
- Subjects with difficulty swallowing tablets or capsules.
- Exclusionary physical and laboratory test findings
- QTc > 475 msec
- Platelets less than or equal to 75,000/mm(3)
- Hemoglobin less than or equal to 9g/dL
- Neutrophils, Absolute less than or equal to 1000/mm(3)
- SGOT (AST) > 3.0 times Upper Limit of Normal
- SGPT (ALT) > 3.0 times Upper Limit of Normal
- Bilirubin 2 times Upper Limit of Normal
- Creatinine greater than or equal to 2mg/dL
- Diastolic blood pressure > 105 mmHg
- TSH > 1.6 times Upper Limit of Normal
- Creatine kinase > 5 times Upper Limit of Normal
- Prohibited treatments
- Regular use of psychotropic medication (antidepressant, lithium,
- antipsychotic, anxiolytic, antiepileptic, opiates, or hypnotics), within one week prior to inclusion, with the exception of benzodiazepines
- administered within the NIAAA program as part of alcohol withdrawal
- treatment. Fluoxetine may not have been taken within 5 weeks, and depot antipsychotics may not have been taken within 12 weeks.
- Any change in a non-excluded medication in the past 3 months.
- Systemic intake of corticosteroids acutely within two weeks or chronically within the last 6 months (Topical hydrocortisone and inhaled corticosteroids are allowed).
- Patients taking medications that are CYP3A4 inhibitors or inducers, should not be taking these medications for at least seven days prior to randomization and during the remainder of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Corticotropin-Releasing Hormone Receptor 1 (CRH1) Antagonism in Anxious Alcoholics
Background:
- Individuals who are dependent on alcohol often have feelings of anxiety, irritability, anger, and depression. These feelings, as well as stress, may contribute to the risk of relapse and continued drinking. Studies have shown that alcohol consumption increases the activity of certain molecules in the brain known as CRH1 receptors, which are key to producing the body s response to stress, and whose activation generates feelings of anxiety. Researchers are interested in learning whether the experimental drug pexacerfont, which blocks CRH1 receptors and has been studied in individuals with anxiety disorders and depression, can lessen anxiety and craving for alcohol as part of alcohol-dependence treatment.
Read more
Objectives:
- To determine the safety and effectiveness of pexacerfont as a treatment for anxiety-related alcohol craving.
Eligibility:
- Individuals between 21 and 65 years of age who are alcohol-dependent and have problems with anxiety.
Design:
- This study requires an inpatient admission to the NIH Clinical Center for approximately 1 month, with two additional study visits 1 week and 1 month after discharge from the hospital.
- Participants will be screened with a medical history, physical examination, and blood and urine tests.
- During the inpatient period, participants will have standard treatment for alcohol dependence, including support and interventions from institute staff to address cravings, anxiety, or other psychological problems. Participants will not receive formal psychological treatment or psychiatric medications for anxiety, but will receive training in relaxation techniques.
- Participants will be assigned to take either pexacerfont or placebo for 3 weeks. During this time, participants will have the following procedures:
- Frequent blood tests.
- Rating scales and questionnaires about alcohol cravings and anxiety.
- Dexamethasone suppression test with frequent blood draws to study hormone response to stress.
- Social stress test involving public speaking, followed by blood samples and questionnaires on alcohol craving.
- Cue Reactivity (CR) session to study cravings and responses to alcohol-based cues.
- Functional magnetic resonance imaging scan to evaluate brain activity while taking the medication or placebo.
- Participants will have two follow-up visits for additional blood tests and questionnaires about the effects of the treatment ^.
Read the detailed description
OBJECTIVE :
To evaluate pexacerfont, an orally available, brain penetrant selective CRH1 antagonist for its ability to modulate emotional and motivational processes in anxious, recently detoxified alcohol dependent patients.
STUDY POPULATION:
Up to 70 anxious, alcohol dependent subjects, aged 21-65 years will be enrolled to complete the study in 50 patients.
DESIGN
Subjects will be inpatients and enter the present protocol once withdrawal treatment, if needed, is completed. They will undergo interviews for construction of guided imagery scripts during a 3 day pre-treatment phase, after which they will receive randomized double blind treatment with active medication or placebo for 23 days, followed by a 3 day post-treatment inpatient monitoring phase, and two follow-up outpatient visits. While hospitalized, repeated measures of spontaneous craving for alcohol, ratings of psychopathology, and blood chemistry including cortisol will be obtained over this time. During the second week of treatment, craving responses will be assessed in a challenge session that combines a social stressor and exposure to physical alcohol cues. During the final week, three sessions of guided imagery will be carried out, on separate days and in a counter-balanced order, exposing the subject to personalized stress-, alcohol- or neutral condition associated stimuli. The final week will also include an fMRI session with emotional and motivational tasks, on a day separate from any guided imagery session. Subjects will remain hospitalized throughout the study, will remain on the unit for a 3 day post-medication monitoring period, and will return for follow up app. 1 and 4 weeks following completion of randomized treatment.
OUTCOME MEASURES
The primary outcome will be craving for alcohol on guided imagery challenge sessions. Secondary outcomes will include craving as measured in the combined social stress alcohol cue challenge session, spontaneous craving and psychopathology ratings repeatedly measured on the inpatient unit over time. Exploratory blood biomarkers and brain responses to positive and negative affective stimuli on the fMRI session will also be obtained.
- Being tested
- Pexacerfont, Placebo
- Keywords
- Addiction, Alcohol, Alcohol Treatment, Alcoholics, Alcohol Dependence, Anxiety Disorder, Alcoholism
- Medical subject headings
- Alcohol-Related Disorders, Alcoholism, Anxiety Disorders, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PexacerfontDrug
300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3.
PlaceboDrug
300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3.
| Study group | Role | What they receive |
|---|---|---|
| Pexacerfont | Active comparator | Pexacerfont was given orally as a loading dose of 300 mg/day for 1 week, followed by 100mg/day for 16-20 days Receives: Drug: Pexacerfont |
| Placebo | Placebo comparator | Oral placebo was given during the 1-week loading dose phase, and during the next 16-20 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes prior to the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 5 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 30 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 45 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 60 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 75 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Alcohol Cue Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 90 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes prior to the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 5 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 15 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 30 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 45 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 60 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 75 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol Craving in Response to the Stress Script
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Measured: 90 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionJul 2014
- Study completionJul 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 (3)Papers the sponsor has linked to this study.
- Other trials for Alcohol-Related DisordersStudies of the same condition, open and under way.
- 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Markus A Heilig, M.D., Principal investigator, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01227980
- Sponsor's protocol ID
- 110010
- Other IDs
- 11-AA-0010
- Status last verified
- Dec 2015
- First submitted
- 22 Oct 2010
- Last updated
- 2 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76. doi: 10.1016/j.pharmthera.2006.02.001. Epub 2006 Mar 20.
PubMed 16545872Epstein DH, Preston KL, Stewart J, Shaham Y. Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology (Berl). 2006 Nov;189(1):1-16. doi: 10.1007/s00213-006-0529-6. Epub 2006 Sep 22.
PubMed 17019567Anton RF, Moak DH, Latham PK. The obsessive compulsive drinking scale: A new method of assessing outcome in alcoholism treatment studies. Arch Gen Psychiatry. 1996 Mar;53(3):225-31. doi: 10.1001/archpsyc.1996.01830030047008.
PubMed 8611059
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Corticotropin-Releasing Hormone Receptor 1 (CRH1) Antagonism in Anxious Alcoholics
- ClinicalTrials.gov ID
- NCT01227980
- Acronym / sponsor ID
- 110010
- Keywords
- Addiction, Alcohol, Alcohol Treatment, Alcoholics, Alcohol Dependence, Anxiety Disorder, Alcoholism
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- Oct 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 25 Oct 2010 (estimated)
- Results
- Posted 10 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Individuals who are dependent on alcohol often have feelings of anxiety, irritability, anger, and depression. These feelings, as well as stress, may contribute to the risk of relapse and continued drinking. Studies have shown that alcohol consumption increases the activity of certain molecules in the brain known as CRH1 receptors, which are key to producing the body s response to stress, and whose activation generates feelings of anxiety. Researchers are interested in learning whether the experimental drug pexacerfont, which blocks CRH1 receptors and has been studied in individuals with anxiety disorders and depression, can lessen anxiety and craving for alcohol as part of alcohol-dependence treatment.
Objectives:
- To determine the safety and effectiveness of pexacerfont as a treatment for anxiety-related alcohol craving.
Eligibility:
- Individuals between 21 and 65 years of age who are alcohol-dependent and have problems with anxiety.
Design:
- This study requires an inpatient admission to the NIH Clinical Center for approximately 1 month, with two additional study visits 1 week and 1 month after discharge from the hospital.
- Participants will be screened with a medical history, physical examination, and blood and urine tests.
- During the inpatient period, participants will have standard treatment for alcohol dependence, including support and interventions from institute staff to address cravings, anxiety, or other psychological problems. Participants will not receive formal psychological treatment or psychiatric medications for anxiety, but will receive training in relaxation techniques.
- Participants will be assigned to take either pexacerfont or placebo for 3 weeks. During this time, participants will have the following procedures:
- Frequent blood tests.
- Rating scales and questionnaires about alcohol cravings and anxiety.
- Dexamethasone suppression test with frequent blood draws to study hormone response to stress.
- Social stress test involving public speaking, followed by blood samples and questionnaires on alcohol craving.
- Cue Reactivity (CR) session to study cravings and responses to alcohol-based cues.
- Functional magnetic resonance imaging scan to evaluate brain activity while taking the medication or placebo.
- Participants will have two follow-up visits for additional blood tests and questionnaires about the effects of the treatment ^.
Detailed description
OBJECTIVE :
To evaluate pexacerfont, an orally available, brain penetrant selective CRH1 antagonist for its ability to modulate emotional and motivational processes in anxious, recently detoxified alcohol dependent patients.
STUDY POPULATION:
Up to 70 anxious, alcohol dependent subjects, aged 21-65 years will be enrolled to complete the study in 50 patients.
DESIGN
Subjects will be inpatients and enter the present protocol once withdrawal treatment, if needed, is completed. They will undergo interviews for construction of guided imagery scripts during a 3 day pre-treatment phase, after which they will receive randomized double blind treatment with active medication or placebo for 23 days, followed by a 3 day post-treatment inpatient monitoring phase, and two follow-up outpatient visits. While hospitalized, repeated measures of spontaneous craving for alcohol, ratings of psychopathology, and blood chemistry including cortisol will be obtained over this time. During the second week of treatment, craving responses will be assessed in a challenge session that combines a social stressor and exposure to physical alcohol cues. During the final week, three sessions of guided imagery will be carried out, on separate days and in a counter-balanced order, exposing the subject to personalized stress-, alcohol- or neutral condition associated stimuli. The final week will also include an fMRI session with emotional and motivational tasks, on a day separate from any guided imagery session. Subjects will remain hospitalized throughout the study, will remain on the unit for a 3 day post-medication monitoring period, and will return for follow up app. 1 and 4 weeks following completion of randomized treatment.
OUTCOME MEASURES
The primary outcome will be craving for alcohol on guided imagery challenge sessions. Secondary outcomes will include craving as measured in the combined social stress alcohol cue challenge session, spontaneous craving and psychopathology ratings repeatedly measured on the inpatient unit over time. Exploratory blood biomarkers and brain responses to positive and negative affective stimuli on the fMRI session will also be obtained.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pexacerfont | Active comparator | Drug: PexacerfontPexacerfont was given orally as a loading dose of 300 mg/day for 1 week, followed by 100mg/day for 16-20 days |
| Placebo | Placebo comparator | Drug: PlaceboOral placebo was given during the 1-week loading dose phase, and during the next 16-20 days |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
Key exclusion criteria (46 listed)
- General:
- Sex and reproductive status:
- administration of the first study drug dose
- Exclusionary psychiatric conditions:
- Exclusionary medical history and concurrent medical conditions:
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 |
|---|---|---|
| Pexacerfont300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3. | Drug | Pexacerfont |
| Placebo300 mg, orally, once/day during week 1, 100 mg, orally, once/day during weeks 2 and 3. | Drug | Placebo |
Primary outcome
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 15 minutes prior to the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 5 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 15 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 30 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 45 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 60 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 75 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Alcohol Cue Script
Time frame: 90 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 15 minutes prior to the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 5 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 15 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 30 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 45 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 60 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 75 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Alcohol Craving in Response to the Stress Script
Time frame: 90 minutes after the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period
Alcohol craving was measured using the Alcohol Urges Questionnaire (AUQ). The AUQ is an 8-item self-administered instrument that assesses craving for alcohol among alcohol users in the current context (i.e., right now). The score ranges from 8 (lowest craving value) to 56 (highest craving value).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16545872Heilig M, Egli M. Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther. 2006 Sep;111(3):855-76. doi: 10.1016/j.pharmthera.2006.02.001. Epub 2006 Mar 20.
- Background: PubMed 17019567Epstein DH, Preston KL, Stewart J, Shaham Y. Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure. Psychopharmacology (Berl). 2006 Nov;189(1):1-16. doi: 10.1007/s00213-006-0529-6. Epub 2006 Sep 22.
- Background: PubMed 8611059Anton RF, Moak DH, Latham PK. The obsessive compulsive drinking scale: A new method of assessing outcome in alcoholism treatment studies. Arch Gen Psychiatry. 1996 Mar;53(3):225-31. doi: 10.1001/archpsyc.1996.01830030047008.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Markus A Heilig, M.D. principal investigator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pexacerfont in people with Alcohol-Related Disorders and Alcohol Dependence, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) 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 12 inclusion and 46 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 2 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. 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 10 Dec 2015). 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?
Alcohol Craving in Response to the Alcohol Cue Script (time frame: 15 minutes prior to the beginning of script presentation, which occurred on Day 24, 25, or 26 of the treatment period). The study lists 16 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 NCT01227980, which also lists 3 linked publications.
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 2 Feb 2016.