Acetate Tracer for Alcohol Consumption

Recruiting at 1 trial location

Overseen By Elizabeth Guidone, B.A.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Disulfiram, Naltrexone, Acamprosate, Anticonvulsants

Disqualifiers: Neurological, Cardiovascular, Endocrine, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how alcohol affects stress and the body's chemistry, with a focus on cortisol, a stress hormone. The researchers aim to find better ways to help people reduce or stop harmful drinking. Participants will undergo brain imaging using deuterium, a special substance that helps measure metabolism. This process involves a deuterated acetate tracer used in deuterium metabolic imaging. The trial seeks individuals who meet criteria for Alcohol Use Disorder (AUD) and are currently drinking at risky levels or have been sober for at least three months. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for alcohol use disorder.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but it excludes those who have recently taken medications that could affect the study, like disulfiram, naltrexone, acamprosate, and anticonvulsants. It's best to discuss your specific medications with the study team.

What prior data suggests that deuterium metabolic imaging with deuterated acetate tracer is safe?

Research has shown that deuterium metabolic imaging, which uses special tracers, is generally safe for people. Deuterium is a natural, non-radioactive substance. Studies have found that it can safely track how the body processes substances without causing harm.

This technique is non-invasive, meaning it doesn't involve surgery or harmful radiation. These tracers help researchers understand how the body converts food and drink into energy. Previous reports have not identified any major side effects, indicating that this method is safe.

In simpler terms, this imaging has been used without serious side effects, making it a safe way to study how alcohol affects stress and metabolism. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using deuterium metabolic imaging with a deuterated acetate tracer to study alcohol consumption because it offers a new way to understand brain metabolism in different drinking behaviors. Unlike traditional treatments that might focus on reducing alcohol intake or managing withdrawal, this method allows scientists to visualize how alcohol affects the brain's metabolism in real-time. By using deuterium, a naturally occurring, non-radioactive form of hydrogen, researchers can safely track metabolic changes without the risks associated with radiation. This innovative approach could lead to a deeper understanding of alcohol's impact on the brain, potentially paving the way for more targeted and effective treatments in the future.

What evidence suggests that deuterium metabolic imaging with deuterated acetate tracer is effective for studying alcohol consumption?

Studies have shown that deuterium metabolic imaging (DMI) is a promising tool for studying how the brain uses energy. This trial will use DMI with a deuterated acetate tracer to observe how the brain processes substances in different participant groups. Research indicates that DMI can safely provide real-time insights into brain metabolism. Although limited data exists on using this imaging method specifically for alcohol-related stress, early findings suggest it might help researchers understand chemical changes in the brain due to alcohol. This understanding could eventually lead to better ways to manage or reduce harmful drinking. ^{1 6 7 8 9}

Who Is on the Research Team?

Graeme Mason, Ph.D.

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for individuals who are sober or have alcohol-related conditions such as Alcohol Use Disorder. Participants should be interested in understanding how their drinking habits affect stress levels and body chemistry.

Inclusion Criteria

Stated willingness to comply with all study procedures and availability for the duration of the study

I am willing to undergo treatment for alcohol use if I'm currently drinking, or I have been sober for 3+ months.

I can read, write, and fill out forms in English.

Exclusion Criteria

Women who are pregnant or nursing. Women who have an IUD that would make imaging unsafe

Current DSM-5 substance use disorder (other than AUD or tobacco use disorder)

Any metallic objects implanted in their body which would make imaging unsafe (pacemaker, etc)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Intake Session

Participants complete an in-person intake session consisting of an interview, questionnaires, lab work, and a urine drug screen

1 day

1 visit (in-person)

Infusion Study

Participants undergo brain imaging with intravenous administration of deuterated sodium acetate to measure rates of metabolism

1 day

1 visit (in-person)

Inpatient Detoxification

Treatment seeking participants undergo an inpatient, medically supervised detoxification

1 week

Inpatient stay

Follow-up

Participants are monitored for changes in alcohol and stress measures, and brain imaging is repeated for treatment seekers

1 month

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Deuterium Metabolic Imaging with deuterated acetate tracer

Trial Overview The study uses Deuterium Metabolic Imaging with a deuterated acetate tracer to investigate the relationship between alcohol consumption, stress hormone cortisol, and body chemistry.

How Is the Trial Designed?

Group I: Treatment Seeking (TS) Experimental Treatment 1 Intervention

Participants will complete an initial telephone screen. Participants to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). If found to be eligible participants will be scheduled for an inpatient admission. Participants will take part in an inpatient, medically supervised detoxification. In early sobriety (normally within one week of the last drink) and after approximately one month, participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.

Group II: Long-Term Recovery (LTS) Experimental Treatment 1 Intervention

Participants will complete an initial telephone screen. Participants found to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). Participants found to be eligible will be scheduled for an infusion study. Participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.

Group III: Light/Non Drinking (LD) Experimental Treatment 1 Intervention

Participants will complete an initial telephone screen. Participants found to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). Participants found to be eligible will be scheduled for an infusion study. Participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.

Group IV: Heavy/Non-Dependent Risky Drinking (HD) Experimental Treatment 1 Intervention

Participants will complete an initial telephone screen. Participants found to be potentially eligible will be scheduled for an in-person Intake Session (consisting of an interview, questionnaires, lab work, and a urine drug screen). Participants found to be eligible will be scheduled for an infusion study. Participants will undergo brain imaging with intravenous administration of deuterated sodium acetate. Deuterium is a naturally occurring, non-radioactive substance that allows us to measure rates of metabolism. Neurocognitive tests will be performed to assess the impact of alcohol drinking.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

A study analyzing brain samples from 74 individuals with a history of heavy alcohol use revealed significant changes in metabolite levels, particularly in the frontal cortex, compared to controls.

Notable alterations included decreased neurotransmitters like GABA and acetylcholine, and increased levels of metabolites related to alcohol metabolism, indicating that heavy alcohol use disrupts brain chemistry and energy metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in the metabolic profile of human male postmortem frontal cortex and cerebrospinal fluid samples associated with heavy alcohol use. Kärkkäinen, O., Kokla, M., Lehtonen, M., et al.[2022]

The study measured the kinetic deuterium isotope effect on ethanol oxidation in various rat and rabbit models, revealing an isotope effect range of 2.66 to 2.93, with a mean of 2.89 in anaesthetized rats, indicating significant activity of alcohol dehydrogenase (ADH) in ethanol metabolism.

The presence of acetaldehyde was found to rapidly decrease the apparent isotope effect, but using the ADH inhibitor isobutyramide helped maintain a constant isotope effect, suggesting that non-ADH pathways contribute minimally (less than 10%) to ethanol oxidation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deuterium isotope effects on ethanol oxidation in perfused rat liver and in rats and rabbits in vivo: application to determine the contribution of various pathways. Lundquist, F., Quistorff, B., Huang, MT.[2019]

Positron emission tomography (PET) studies have revealed that alcohol's rewarding effects are linked to changes in various neurotransmitter systems, including dopamine and GABA, as well as its caloric properties, which contribute to alcohol use disorders (AUD).

Research has shown that chronic alcohol exposure leads to significant alterations in brain metabolism and neurotransmitter function, which are associated with compulsive drinking and withdrawal symptoms, highlighting the potential for PET imaging to inform treatment strategies for AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurochemical and metabolic effects of acute and chronic alcohol in the human brain: Studies with positron emission tomography. Volkow, ND., Wiers, CE., Shokri-Kojori, E., et al.[2018]

Acute ethanol administration significantly decreased local cerebral glucose utilization (LCGU) in specific brain regions of adolescent alcohol-preferring (P) rats, indicating altered neuronal activity due to alcohol exposure.

Adolescent P rats showed higher baseline LCGU rates compared to nonpreferring (NP) rats, suggesting that their heightened sensitivity to ethanol may contribute to their increased alcohol consumption behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute ethanol effects on local cerebral glucose utilization in select central nervous system regions of adolescent alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. Strother, WN., Lumeng, L., McBride, WJ.[2021]

A new method was developed to evaluate the kinetic isotope effect (KIE) of deuterated drugs by incubating both deuterated and non-deuterated forms together in liver microsomal assays, allowing for direct comparison without complex separation techniques.

In a proof-of-concept study using the neuroinflammation imaging agent PBR111, the method confirmed that deuteration at an inactive site did not significantly affect the drug's kinetics, demonstrating the potential for site-specific deuteration to optimize drug properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A rapid MS/MS method to assess the deuterium kinetic isotope effect and associated improvement in the metabolic stability of deuterated biological and pharmacological molecules as applied to an imaging agent. Murphy, RB., Wyatt, NA., Fraser, BH., et al.[2019]

Positron emission tomography (PET) is a powerful imaging technique that can detect early functional brain changes due to alcohol consumption, even before structural damage occurs.

Research using PET has shown that cognitive functions can gradually recover with continued abstinence from alcohol, and it has also provided insights into the mechanisms of alcohol's effects and the genetic factors related to alcoholism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring the Brain's Response to Alcohol With Positron Emission Tomography. Volkow, N., Wang, GJ., Doria, JJ.[2020]

Positron emission tomography (PET) is a highly sensitive imaging technology that can measure the concentration and distribution of radiotracers in the brain, allowing researchers to study neurochemical and metabolic processes without disrupting the system being measured.

PET has been effectively used to investigate the effects of alcohol and other drugs on brain function and neurochemistry in both humans and nonhuman primates, with new microPET technology enabling similar studies in rodents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography as a tool for studying alcohol abuse. Thanos, PK., Wang, GJ., Volkow, ND.[2021]

Stable isotopically labelled substrates are safe and effective for tracking metabolic processes in vivo, particularly in children and adults, allowing for precise measurement of biological compounds.

Applications of stable isotopes in clinical medicine include non-invasive tests like the 13C-breath tests for diagnosing Helicobacter pylori and assessing gastrointestinal functions, highlighting their utility in understanding metabolic dynamics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo research with stable isotopes in biochemistry, nutrition and clinical medicine: an overview. de Meer, K., Roef, MJ., Kulik, W., et al.[2008]

Chronic ethanol abuse leads to the formation of nonoxidative metabolites, such as ethyl glucuronide and phosphatidylethanol, which persist in the body longer than ethanol itself and can serve as biomarkers for alcohol intake.

These nonoxidative metabolites, although produced in smaller amounts, can significantly impact cellular signaling and organelle function, potentially contributing to the toxicity associated with ethanol consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonoxidative ethanol metabolism in humans-from biomarkers to bioactive lipids. Heier, C., Xie, H., Zimmermann, R.[2023]

Acute alcohol consumption leads to dopamine (DA) release in the ventral striatum of social drinkers, indicating a normal response of the dopaminergic system.

In individuals with alcohol use disorder (AUD), this DA release is impaired, and they show reduced availability of dopamine D2 and D3 receptors, which may contribute to the disorder's development and persistence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dopamine and Alcohol: A Review of in vivo PET and SPECT Studies. Spitta, G., Garbusow, M., Buchert, R., et al.[2023]

In a study using [18F]-FDG microPET imaging on alcohol-drinking rats, it was found that alcohol significantly reduces overall brain glucose metabolism, particularly in the parietal cortex and cerebellum, indicating a direct impact of alcohol on brain function.

Long-term alcohol consumption leads to tolerance, as evidenced by diminished effects on glucose metabolism in long-term drinkers compared to alcohol-naïve and short-term drinkers, while some brain regions showed increased activity, suggesting complex changes in brain function during addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism. Gispert, JD., Figueiras, FP., Vengeliene, V., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11144684/

Advances and prospects in deuterium metabolic imaging (DMI) Deuterium metabolic imaging (DMI) has emerged as a promising non-invasive technique for studying metabolism in vivo.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8470013/

Deuterium Metabolic Imaging—Rediscovery of a ... Safety: Deuterated molecules have been studied in humans for many years, especially water itself (D2O) [75,76,77,78,79]. Deuterium was shown to be lethal when ...

3. researchgate.net researchgate.net/publication/381119204_Advances_and_prospects_in_deuterium_metabolic_imaging_DMI_a_systematic_review_of_in_vivo_studies

(PDF) Advances and prospects in deuterium metabolic ... Background Deuterium metabolic imaging (DMI) has emerged as a promising non-invasive technique for studying. metabolism in vivo.

4. researchgate.net researchgate.net/publication/348698024_Deuterium_Metabolic_Imaging_of_the_Healthy_and_Diseased_Brain

(PDF) Deuterium Metabolic Imaging of the Healthy and ... In this review we highlight deuterium metabolic imaging (DMI) as a novel translational technique for assessment of brain metabolism, with ...

5. pdfs.semanticscholar.org pdfs.semanticscholar.org/9f2d/b11ee4f74bf05eff9ae75010ef3d7cfc63b0.pdf?skipShowableCheck=true

Deuterium in drug discovery The changes in metabolic pathways are not always predictable and therefore are measured by in vitro and/or in vivo metabolism studies. For example, caffeine ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8083995/

Deuterium Metabolic Imaging – Back to the Future - PMC Deuterium metabolic spectroscopy (DMS) and imaging (DMI) have recently been described as simple and robust MR-based methods to map metabolism.

7. analyticalsciencejournals.onlinelibrary.wiley.com analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/nbm.70121

Probing Intracellular Yeast Metabolism With Deuterium ... Deuterium magnetic resonance spectroscopy (DMRS) provides a straightforward, noninvasive method for monitoring real-time metabolic flux.

8. medicine.yale.edu medicine.yale.edu/biomedical-imaging-institute/research/brain/

Brain < Yale Biomedical Imaging Institute This finding has implications for alcohol detoxification: when someone stops drinking, they lose not only the alcohol, but the acetate that comes from the ...

9. mdpi.com mdpi.com/2218-1989/11/9/570

Deuterium Metabolic Imaging—Rediscovery of a ... A robust method based on administration of a substrate (glucose, acetate, fumarate, etc.) labeled with the stable isotope of hydrogen and the observation of ...