Ignite Creation Date:
2024-05-05 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00106106
Status:
COMPLETED
Last Update Posted:
2012-01-12
First Post:
2005-03-19
Brief Title:
Acamprosate to Reduce Symptoms of Alcohol Withdrawal
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Acamprosate for Central Nervous System Hyperexcitability and Neuroadaptation in Alcohol Withdrawal
Status:
COMPLETED
Status Verified Date:
2012-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 pm 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
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 pm 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
Detailed Description:
Objective Clinical as well as preclinical studies indicate that the process of developing alcohol dependence recruits a progressively aggravated hyperglutamatergic state which in turn is a key signal for emotional dysregulations leading to craving and relapse as well as neurotoxicity leading to cognitive impairment and loss of grey matter in alcoholic patients Acamprosate has recently been approved for relapse prevention in sober alcoholics an effect mediated through largely unknown mechanisms Preclinical data indicate however that it might primarily be useful for targeting the hyperglutamatergic state that develops during recurring withdrawal episodes halting the process described above If so acamprosate might be of value as a withdrawal treatment to prevent the progression of alcohol dependence The aim of the present protocol is to evaluate in a randomized controlled trial the effects of acamprosate during withdrawal and the early post-withdrawal phase The primary outcome variable will be central glutamateglutamine concentration as determined by MR spectroscopy A number of exploratory biological and clinical measures will in addition be obtained and used for secondary analyses as specified below
Study Population We will study patients age 21 - 65 without gross impairment of judgment or complicated psychiatric or other morbidity going into withdrawal or with a high probability of doing so will be admitted as inpatients to the NIAAA CC-unit A group of healthy volunteers who do not receive study medication will be examined separately in order to confirm that a hyperglutamatergic state is present in the patients during withdrawal
Design All patients will receive standard care for alcohol detoxification In addition half of them will be randomized in a blinded fashion to oral acamprosate two 333 mg tablets taken 3 times daily or corresponding placebo Validated rating scales CIWA-Ar CPRS-SA will be used to assess intensity of withdrawal and psychopathology If severity of withdrawal exceeds a predefined criterion standard diazepam treatment will be added to study medication The accrual target is based on a primary analysis sample of patients who will not require diazepam medication which is a potential confound A secondary analysis will be carried out on the complete sample analyzing the requirement foramount of diazepam supplement as a secondary outcome variable
Outcome Measures A battery of tests will be obtained during the 1st and 3rd week of inpatient treatment These will include NMR-spectroscopy to quantify central levels of excitatory and inhibitory amino acids primary outcome variable GluX concentration lumbar puncture to obtain CSF for analysis of neurotransmitterneurohormone metabolites and synaptic proteins Repeated 4 x daily blood collection for analysis of serum cortisol and ACTH will be obtained to assess spontaneous activity and circadian variation of the HPA-axis and the combined dexamethasone - CRH test will be carried out to dynamically probe this system and gauge its sensitivity for feedback inhibition
Study Population We will study patients age 21 - 65 without gross impairment of judgment or complicated psychiatric or other morbidity going into withdrawal or with a high probability of doing so will be admitted as inpatients to the NIAAA CC-unit A group of healthy volunteers who do not receive study medication will be examined separately in order to confirm that a hyperglutamatergic state is present in the patients during withdrawal
Design All patients will receive standard care for alcohol detoxification In addition half of them will be randomized in a blinded fashion to oral acamprosate two 333 mg tablets taken 3 times daily or corresponding placebo Validated rating scales CIWA-Ar CPRS-SA will be used to assess intensity of withdrawal and psychopathology If severity of withdrawal exceeds a predefined criterion standard diazepam treatment will be added to study medication The accrual target is based on a primary analysis sample of patients who will not require diazepam medication which is a potential confound A secondary analysis will be carried out on the complete sample analyzing the requirement foramount of diazepam supplement as a secondary outcome variable
Outcome Measures A battery of tests will be obtained during the 1st and 3rd week of inpatient treatment These will include NMR-spectroscopy to quantify central levels of excitatory and inhibitory amino acids primary outcome variable GluX concentration lumbar puncture to obtain CSF for analysis of neurotransmitterneurohormone metabolites and synaptic proteins Repeated 4 x daily blood collection for analysis of serum cortisol and ACTH will be obtained to assess spontaneous activity and circadian variation of the HPA-axis and the combined dexamethasone - CRH test will be carried out to dynamically probe this system and gauge its sensitivity for feedback inhibition
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-AA-0120 | OTHER | National Institutes of Health | None |