Phase 2
Completed N=44
CRF1 Antagonist GSK561679 in Alcoholism
Source: ClinicalTrials.gov NCT01187511 ↗Enrolled (actual)
44
Serious AEs
0.0%
Results posted
Nov 2016
Primary outcomePrimary: Alcohol Craving in Response to the Alcohol Cue Script — 11.6932; 14.6126 Units on a scale
Summary
Objective:
To evaluate GSK561679, an orally available, brain penetrant selective CRH1 antagonist for its ability to reduce alcohol craving in recently detoxified alcohol dependent women in response to stress or alcohol-associated stimuli.
Study population:
Up to 60 anxious, alcohol dependent women, aged 21-65 years will be enrolled to complete the study in 50 patients.
Background:
* Anxiety, irritability, anger, and depression can all cause stress that may lead to continued drinking in heavy drinkers. One way the brain responds to stress is through a protein on brain cells called a CRH receptor. Previous research has shown that the CRH receptor is involved in negative emotional states and that chronic alcohol consumption increases the activity of CRH receptors in the brain. Medications that block CRH receptors can decrease stress-triggered alcohol consumption.
* GSK561679, an experimental drug that blocks the CRH receptors, can reduce negative emotions such as anxiety and a person s desire for alcohol. By looking at the brain s response to stress and the study drug using functional magnetic resonance imaging (fMRI) scans, researchers hope to learn whether GSK561679 can be an effective treatment for stress-related alcohol abuse.
Objectives:
- To evaluate the usefulness of GSK561679 in reducing stress-related alcohol craving in alcohol-dependent women.
Design:
* Participants in the study will be enrolled in the standard NIH treatment program for alcohol dependence, and will be required to stay at the NIH inpatient treatment unit for an additional 31 days.
* Participants will receive either the study medication or a placebo to be taken once a day in the evening for 4 weeks.
* Participants will have the following procedures while on the study medication:
* Questionnaires about alcohol craving, depression, and anxiety.
* Recordings and responses to personal emotional reactions to stressful, nonstressful, and alcohol-related situations, with blood samples taken during the responses.
* Regular blood tests to measure stress hormones in the blood.
* Speech preparation and presentation (Trier test), along with blood samples, to measure stress hormones in the blood.
* Sessions to measure responses to alcohol-related cues.
* Functional magnetic resonance imaging (fMRI) scans.
* Participants will return for follow-up visits 1 week and 1 month after stopping the study drug and being discharged from the study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Alcohol Craving in Response to the Alcohol Cue Script |
8.9075; 13.1841 | — |
| PRIMARY Alcohol Craving in Response to the Stress Script |
13.1376; 10.0004 | — |
| SECONDARY Alcohol Craving in Response to the Trier/Cue-reactivity Procedure |
13.7895; 13.0592 | — |
| SECONDARY Anxiety Symptom Ratings Measured Bi-weekly During the Treatment Period |
6.6078; 6.66 | — |
| SECONDARY Depression Symptom Ratings Measured Bi-weekly During the Treatment Period |
6.6366; 6.9188 | — |
| SECONDARY Spontaneous Alcohol Craving Measured Bi-weekly During the Treatment Period |
8.1286; 8.7942 | — |
Eligibility Criteria
- INCLUSION CRITERIA:
DSM-IV diagnosis of alcohol dependence on SCID interview (23), alcohol problems as primary complaint among substance use disorders, and alcohol use within the last month.
Female sex
Spielberger trait anxiety inventory (24) score >39.
Age 21 65 years.
Able to comprehend the consent form, and provide informed consent.
Either:
- of non-childbearing potential defined as pre-menopausal (for definition, see appendix females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol 5 times the upper limit of normal (ULN), aspartate aminotransferase (AST) > 3 times ULN, alanine transaminase (ALT) > 3 times the ULN or Alkaline Phosphatase > 1.5 ULN; total bilirubin >1.5 times the ULN or direct bilirubin > 35%; Albumin below 3 g/dL; INR > 1.5;
- On the day preceding active medication: Alkaline Phosphatase > ULN, AST > 2 times ULN, ALT > 2 times the ULN or GGT > 4 times the ULN, total bilirubin >1.5 times the ULN or direct bilirubin > 35%; Albumin below3 g/dL; INR > 1.5; if, on the day preceding active medication,
- On the day preceding active medication, any of the liver function tests above have increased more than 1 time the ULN over the value at the screening.
- Any cardiovascular condition, including uncontrolled hypertension, or ECG abnormality that, in the investigator s judgment, may pose a safety concern; specifically, ECG finding of a QTc time > 450 msec unless normalized on repeat ECG.
- Subjects with known or suspected iron deficiency of unknown etiology.
- Positive pregnancy test, lactating, or planning to become pregnant within 8 weeks from the start of this 4-week study.
- Regular use of psychotropic medication (antidepressant, lithium, antipsychotic, anxiolytic, antiepileptic, opiates, or hypnotics), within one week, 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.
- Current use, or likely requirement during the study, or use of within preceding 4 weeks, of contraindicated medications as listed in Appendix III and 2 weeks for incidental use of non-steroid anti-inflammatory drugs (NSAIDs).
- Subjects maintained on thyroid medication must have been euthyroid for at least six months.
- Systemic intake of corticosteroids acutely within two weeks or chronically within the last 6 months (Topical hydrocortisone and inhaled corticosteroids are allowed).
- A history of allergic reaction to, or significant adverse effects from excipients in the GSK561679 tablet (see GSK561679 Investigator Brochure).
Data sourced from ClinicalTrials.gov (NCT01187511). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.