Acamprosate to Reduce Symptoms of Alcohol Withdrawal
Status:
Completed
Trial end date:
2010-07-01
Target enrollment:
Participant gender:
Summary
This study will examine whether a new drug called acamprosate can be helpful for alcohol
withdrawal, a result of drinking high amounts of alcohol for long periods of time. Alcohol
withdrawal can cause various symptoms, including nausea or vomiting, anxiety or depression,
tremor, high blood pressure, and others. During withdrawal, brain chemicals called
neurotransmitters change, with some rising to abnormally high levels. These changes may
contribute to alcohol craving, drinking relapse and impaired mental performance. This study
will see if taking acamprosate for 4 weeks can lower the levels of neurotransmitters, such as
glutamate, lessen withdrawal symptoms and decrease alcohol craving and brain damage
associated with withdrawal.
Healthy normal volunteers and alcohol-dependent patients between 21 and 65 years of age may
be eligible for this study.
Participants are admitted to the hospital for 28 days. They receive standard inpatient care
for alcohol detoxification, including a medical history and physical examination,
neurological evaluation, laboratory tests, nursing, nutrition, discharge planning and
referrals for treatment of concomitant conditions, if needed. In addition, they are randomly
assigned to take either two acamprosate or two placebo pills three times a day for 28 days
and undergo the following tests and procedures:
- Days 1-28: Drug treatment. Patients take acamprosate or placebo daily. Patients with
severe withdrawal symptoms may also receive diazepam (Valium). Throughout their
hospitalization, patients fill out questionnaires about their emotional state and
personality and are interviewed by staff about their mental health, use of alcohol,
cigarettes, and illicit drugs, employment, support systems and family and social
relationships, and their legal status.
- Days 2 and 3: Blood tests. Blood is tested for levels of the stress hormones cortisol
and ACTH, which are released to excess during alcohol withdrawal. For this test, a
heparin lock (thin, flexible plastic tube with a rubber stopper on the end) is placed in
an arm vein for blood collections each day at 6 AM, 12 noon, 6 PM and 12 midnight.
Patients rest in bed for 30 minutes before each collection.
- Day 4: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). These
procedures are done at the same time. They use a strong magnetic field and radio waves
to show structural and chemical changes in the brain. The patient lies on a table in a
space enclosed by a metal cylinder (the scanner) for about 20 to 30 minutes during the
test.
- Day 5: Lumbar puncture (spinal tap). A local anesthetic is given to numb the area for
the procedure. Then, a needle is inserted in the space between the bones in the lower
back where the cerebrospinal fluid circulates below the spinal cord. A small amount of
fluid is collected through the needle.
- Days 5 and 6: Dexamethasone-corticotropin releasing factor (CRF) test. This test
measures the effect of alcohol withdrawal on ACTH and cortisol. The patient takes a
standard dose of the steroid dexamethasone at 11 PM on day 5. At noon the next day, they
are given lunch and then stay in bed and rest. A plastic tube is put in an arm vein. A
salt water solution is slowly infused through the catheter and a blood sample is
withdrawn through it. At 3 p.m., the patient is given 100 micrograms of the hormone CRF.
Repeated blood samples are obtained to measure ACTH and cortisol.
- Days 23-27: All of the tests done on days 2-6 are repeated, except the MRI. MRS is
repeated to measure neurotransmitters.
Phase:
Phase 2
Details
Lead Sponsor:
National Institutes of Health Clinical Center (CC)
Collaborator:
National Institute on Alcohol Abuse and Alcoholism (NIAAA)