MetabolismNCT00070577
Influence of Age and Sex on Alcohol Metabolism and Acute Responses
An observational study of Metabolism, run by National Institute on Alcohol Abuse and Alcoholism (NIAAA) at 1 site in United States.
Trial summary
This study will examine age and sex differences in alcohol metabolism and the effects of alcohol. Men and women differ in their ability to metabolize alcohol, possibly due to differences between men and women in lean body mass, liver size, or the activity of enzymes that act on alcohol in the liver. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Metabolism
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 2003to 3 May 2011
- Phase
- Observational
- Are there results?
- None posted in the registry
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
- This study will be conducted in social drinkers with no current or past history of alcohol dependence or alcohol abuse. Inclusion criteria include:
- Male and female participants between 21-25 years or 55-65 years of age.
- Good health as determined by medical history, physical exam, EKG and lab tests.
- Current non-smokers. Participants who quit smoking for over 1 year can be included.
- Family-history negative, i.e., no family history of alcoholism in the first-or second-degree.
- Young women will have normal menstrual cycles and will be tested during the follicular phase of their cycle (within 7 days of offset of menses) and must have a negative urine pregnancy (hCG) test at the start of each study session.
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- Older women will be post-menopausal, with cessation of menses for at least 12 months prior to enrollment into the study, and a serum follicle stimulating hormone (FSH) level greater than 40 IU/L.
- All participants must report the absence of flushing either currently or in the past, based on the Alcohol Flushing Questionnaire, assessed during screening.
- Participants must have no ferromagnetic objects in their bodies which might be adversely affected by MRI (e.g. surgical clips; metal fragments in any part of the body; cardiac or neurological pacemaker; cochlear or eye implant) - any doubt about presence of these objects will result in exclusion from this study.
Who cannot join
- Current or prior history of any disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening.
- Current history of Axis-I psychiatric illness.
- Current or prior history of any alcohol or drug dependence or abuse, as well as non-drinkers (alcohol-naive individuals or current abstainers).
- Alcohol use exceeding 14 drinks/week for males and 7 drinks/week for females, and use of more than 4 drinks on any one occasion in the 6 months prior to the study.
- Positive result on urine drug screen.
- Pregnancy or intention to become pregnant for women. Female participants will undergo a urine beta-hCG test to ensure they are not pregnant.
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- Use of oral contraceptive pills in younger female participants and use of hormone replacement therapy in older female participants.
- Menstrual cycle irregularities in younger female participants.
- Use of prescription or OTC medications known to interact with alcohol within 2 weeks of the study. These include, but may not be limited to: isosorbide, nitroglycerine, benzodiazepines, warfarin, cough-and-cold preparations which contain anti-histamines, codeine and/or acetaminophen, anti-depressants such as amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as glyburide, metformin and tolbutamide, H2-antagonists for heartburn such as cimetidine and ranitidine, muscle relaxants, pain medicines and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib and naproxen, anti-epileptics including phenytoin and phenobarbital and narcotics including darvocet, percocet and hydrocodone. Drugs known to inhibit or induce enzymes that metabolize alcohol should not be used for 4 weeks prior to the study. These include acetaminophen, chlorzoxazone, isoniazid, metronidazole and disulfiram.
- Exclusions also include herbal preparations containing soy isoflavones (which may have estrogenic properties).
- Inability to undergo the MRI scan for liver volume due to claustrophobia or anxiety when confined to small spaces such as the magnet bore, or due to the presence of metallic implants.
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
This study will examine age and sex differences in alcohol metabolism and the effects of alcohol. Men and women differ in their ability to metabolize alcohol, possibly due to differences between men and women in lean body mass, liver size, or the activity of enzymes that act on alcohol in the liver. Also, older men and women are thought to be more sensitive to alcohol, although the reasons for this are not clear.
Healthy men and women between 21 and 25 years of age and between 55 and 65 years of age who are social drinkers may be eligible for this study. Candidates will be screened with questionnaires about their general and mental health, alcohol use, and family history of alcohol use and problems. They will have a physical examination, electrocardiogram (EKG), routine blood tests, urinalysis to test for drugs of abuse, and a blood test to study the gene responsible for enzymes that metabolize alcohol. Younger women will have a urine pregnancy test and older women will have a test to confirm post-menopausal status.
Read more
Participants will have two study sessions at the NIH Clinical Center outpatient clinic. They come to the clinic by taxi and, upon arrival, take a breathalyzer test for any measurable alcohol levels. They are then given breakfast, after which two catheters (plastic tubes) are placed, one in a vein in each arm. One tube is used to collect blood samples for measuring hormone levels; the other is for infusing alcohol. The infusion is adjusted so that the breath alcohol level is held constant for about 3 hours at a moderate level. Baseline measurements are taken before the infusion begins. During and after the infusion, the participants fill out questionnaires about their moods and feelings. Breath alcohol level and heart rate measurements are monitored frequently. After the test, participants remain in the clinic until their breath alcohol level drops below 0.02 g/L (generally 2 to 3 hours after the infusion stops). They are given lunch and then sent home in a taxi.
Participants also undergo a dual energy x-ray absorptiometry (DEXA) scan to determine lean body mass and a magnetic resonance imaging (MRI) scan of the abdomen to determine liver size. For the DEXA scan, the subject lies still on a table for about 30 minutes while the whole body is scanned using a small amount of radiation. For the MRI, the subject lies in a narrow metal cylinder (the scanner) about 30 minutes for the scan.
Read the detailed description
Previous studies, including our studies using the alcohol clamp, have shown that alcohol pharmacokinetics differ between women and men. Some of the factors that may contribute to these sex differences in absorption, distribution and metabolism include variation in lean body mass (and total body water), liver size and differences in activity or capacity of alcohol metabolizing enzymes in the stomach and livers of women and men. A fundamental difference between men and women is in the levels of the sex hormones estrogen and testosterone, which can influence several of the above factors. Sex differences in alcohol pharmacokinetics, and estrogen itself, have been postulated as determinants of the increased susceptibility of women to alcohol-related liver disease. An additional area of interest is sex- and age-related differences in sensitivity to the effects of alcohol. The elderly are thought to be more sensitive to alcohol and show greater impairment than younger individuals. However, it is not clear if these changes are due to pharmacokinetic or pharmacodynamic factors.
The objectives of this project are (I) to evaluate the influence of age and sex on alcohol elimination rates in men and women, and (II) to determine the influence of age and sex on the initial response and acute adaptation to alcohol on measures of subjective perceptions of alcohol effects and heart rate. This study will be conducted in 24 young and 24 older participants, with equal numbers of males and females in each group. Comparison of alcohol elimination rates across these groups and correlation with liver volume and sex steroid levels will provide a means to examine the influence of sex hormones, estrogen and testosterone, in age-related and sex-related differences in alcohol metabolism and liver volume. This study will examine age- and sex- related differences in response to alcohol on subjective measures of intoxication and mood, as well as on heart-rate and psychophysiological responses to emotional visual stimuli (pictures). This study will also evaluate the effect of acute alcohol administration on gene expression in peripheral blood cells. Findings from these studies will provide important new data regarding the role of sex steroids (estrogen and testosterone) on the metabolism of alcohol, and a better understanding of age- and sex-related differences in metabolic processes that may underlie medically important differences in the responses of individuals to alcohol.
- Conditions
- Metabolism
- Keywords
- Alcohol Clamp, Pharmacokinetics, Pharmacodynamics, Alcohol, Metabolism, Response, Age, Sex, Healthy Volunteer, HV
- Medical subject headings
- Coitus
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2003 (estimated)
- Study start29 Sep 2003
- Study completion3 May 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MetabolismStudies 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
- Observational
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00070577
- Sponsor's protocol ID
- 030283
- Other IDs
- 03-AA-0283
- Status last verified
- 3 May 2011
- First submitted
- 3 Oct 2003
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Aasmoe L, Aarbakke J. Sex-dependent induction of alcohol dehydrogenase activity in rats. Biochem Pharmacol. 1999 May 1;57(9):1067-72. doi: 10.1016/s0006-2952(99)00003-9.
PubMed 10796077Ammon E, Schafer C, Hofmann U, Klotz U. Disposition and first-pass metabolism of ethanol in humans: is it gastric or hepatic and does it depend on gender? Clin Pharmacol Ther. 1996 May;59(5):503-13. doi: 10.1016/S0009-9236(96)90178-2.
PubMed 8646821Ayabe T, Tsutsumi O, Sakai H, Yoshikawa H, Yano T, Kurimoto F, Taketani Y. Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocr J. 1997 Jun;44(3):419-24. doi: 10.1507/endocrj.44.419.
PubMed 9279518
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Age and Sex on Alcohol Metabolism and Acute Responses
- ClinicalTrials.gov ID
- NCT00070577
- Acronym / sponsor ID
- 030283
- Conditions
- Metabolism
- Keywords
- Alcohol Clamp, Pharmacokinetics, Pharmacodynamics, Alcohol, Metabolism, Response, Age, Sex
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)US National Institutes of Health
- Study start
- 29 Sep 2003
- Study completion
- 3 May 2011
- First posted
- 6 Oct 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine age and sex differences in alcohol metabolism and the effects of alcohol. Men and women differ in their ability to metabolize alcohol, possibly due to differences between men and women in lean body mass, liver size, or the activity of enzymes that act on alcohol in the liver. Also, older men and women are thought to be more sensitive to alcohol, although the reasons for this are not clear.
Healthy men and women between 21 and 25 years of age and between 55 and 65 years of age who are social drinkers may be eligible for this study. Candidates will be screened with questionnaires about their general and mental health, alcohol use, and family history of alcohol use and problems. They will have a physical examination, electrocardiogram (EKG), routine blood tests, urinalysis to test for drugs of abuse, and a blood test to study the gene responsible for enzymes that metabolize alcohol. Younger women will have a urine pregnancy test and older women will have a test to confirm post-menopausal status.
Participants will have two study sessions at the NIH Clinical Center outpatient clinic. They come to the clinic by taxi and, upon arrival, take a breathalyzer test for any measurable alcohol levels. They are then given breakfast, after which two catheters (plastic tubes) are placed, one in a vein in each arm. One tube is used to collect blood samples for measuring hormone levels; the other is for infusing alcohol. The infusion is adjusted so that the breath alcohol level is held constant for about 3 hours at a moderate level. Baseline measurements are taken before the infusion begins. During and after the infusion, the participants fill out questionnaires about their moods and feelings. Breath alcohol level and heart rate measurements are monitored frequently. After the test, participants remain in the clinic until their breath alcohol level drops below 0.02 g/L (generally 2 to 3 hours after the infusion stops). They are given lunch and then sent home in a taxi.
Participants also undergo a dual energy x-ray absorptiometry (DEXA) scan to determine lean body mass and a magnetic resonance imaging (MRI) scan of the abdomen to determine liver size. For the DEXA scan, the subject lies still on a table for about 30 minutes while the whole body is scanned using a small amount of radiation. For the MRI, the subject lies in a narrow metal cylinder (the scanner) about 30 minutes for the scan.
Detailed description
Previous studies, including our studies using the alcohol clamp, have shown that alcohol pharmacokinetics differ between women and men. Some of the factors that may contribute to these sex differences in absorption, distribution and metabolism include variation in lean body mass (and total body water), liver size and differences in activity or capacity of alcohol metabolizing enzymes in the stomach and livers of women and men. A fundamental difference between men and women is in the levels of the sex hormones estrogen and testosterone, which can influence several of the above factors. Sex differences in alcohol pharmacokinetics, and estrogen itself, have been postulated as determinants of the increased susceptibility of women to alcohol-related liver disease. An additional area of interest is sex- and age-related differences in sensitivity to the effects of alcohol. The elderly are thought to be more sensitive to alcohol and show greater impairment than younger individuals. However, it is not clear if these changes are due to pharmacokinetic or pharmacodynamic factors.
The objectives of this project are (I) to evaluate the influence of age and sex on alcohol elimination rates in men and women, and (II) to determine the influence of age and sex on the initial response and acute adaptation to alcohol on measures of subjective perceptions of alcohol effects and heart rate. This study will be conducted in 24 young and 24 older participants, with equal numbers of males and females in each group. Comparison of alcohol elimination rates across these groups and correlation with liver volume and sex steroid levels will provide a means to examine the influence of sex hormones, estrogen and testosterone, in age-related and sex-related differences in alcohol metabolism and liver volume. This study will examine age- and sex- related differences in response to alcohol on subjective measures of intoxication and mood, as well as on heart-rate and psychophysiological responses to emotional visual stimuli (pictures). This study will also evaluate the effect of acute alcohol administration on gene expression in peripheral blood cells. Findings from these studies will provide important new data regarding the role of sex steroids (estrogen and testosterone) on the metabolism of alcohol, and a better understanding of age- and sex-related differences in metabolic processes that may underlie medically important differences in the responses of individuals to alcohol.
Study design
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- This study will be conducted in social drinkers with no current or past history of alcohol dependence or alcohol abuse. Inclusion criteria include:
- Male and female participants between 21-25 years or 55-65 years of age.
- Good health as determined by medical history, physical exam, EKG and lab tests.
- Current non-smokers. Participants who quit smoking for over 1 year can be included.
- Family-history negative, i.e., no family history of alcoholism in the first-or second-degree.
Key exclusion criteria (11 listed)
- Current or prior history of any disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening.
- Current history of Axis-I psychiatric illness.
- Current or prior history of any alcohol or drug dependence or abuse, as well as non-drinkers (alcohol-naive individuals or current abstainers).
- Alcohol use exceeding 14 drinks/week for males and 7 drinks/week for females, and use of more than 4 drinks on any one occasion in the 6 months prior to the study.
- Positive result on urine drug screen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 10796077Aasmoe L, Aarbakke J. Sex-dependent induction of alcohol dehydrogenase activity in rats. Biochem Pharmacol. 1999 May 1;57(9):1067-72. doi: 10.1016/s0006-2952(99)00003-9.
- Background: PubMed 8646821Ammon E, Schafer C, Hofmann U, Klotz U. Disposition and first-pass metabolism of ethanol in humans: is it gastric or hepatic and does it depend on gender? Clin Pharmacol Ther. 1996 May;59(5):503-13. doi: 10.1016/S0009-9236(96)90178-2.
- Background: PubMed 9279518Ayabe T, Tsutsumi O, Sakai H, Yoshikawa H, Yano T, Kurimoto F, Taketani Y. Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocr J. 1997 Jun;44(3):419-24. doi: 10.1507/endocrj.44.419.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metabolism, 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 9 inclusion and 11 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 Jul 2017. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00070577, 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 Jul 2017.