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

Trial Summary

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 data supports the effectiveness of the treatment Deuterium Metabolic Imaging with deuterated acetate tracer for alcohol consumption?

Positron emission tomography (PET) has been used to study the effects of alcohol on brain function, showing changes in brain metabolism and neurotransmitter activity. PET studies have documented alterations in brain energy utilization, including glucose and acetate metabolism, which are relevant to understanding alcohol use disorders. ^{1 2 3 4 5}

Is the deuterated acetate tracer safe for human use?

The research does not provide specific safety data for the deuterated acetate tracer in humans, but deuterium-labeled compounds have been used in other studies and are generally considered safe when used in small amounts for imaging purposes. ^{1 2 6 7 8}

How does the acetate tracer treatment for alcohol consumption differ from other treatments?

The acetate tracer treatment is unique because it uses a special imaging technique called positron emission tomography (PET) to study how alcohol affects brain function and metabolism. This approach allows researchers to observe changes in the brain at very precise levels, which is different from traditional treatments that focus on reducing alcohol consumption or managing withdrawal symptoms. ^{1 2 9 10 11}

What is the purpose of this trial?

The purpose of this study is to learn how drinking alcohol affects how people experience stress and how that is affected by the body's chemistry. Specifically, the investigators will be studying relationships of drinking and a stress hormone called cortisol. The investigators believe that results will lead us to find more effective ways to help people stop or reduce drinking when participants are drinking at harmful levels.

Research Team

Graeme Mason, Ph.D.

Principal Investigator

Yale University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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) 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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Positron emission tomography as a tool for studying alcohol abuse. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Dopamine and Alcohol: A Review of in vivo PET and SPECT Studies. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Monitoring the Brain's Response to Alcohol With Positron Emission Tomography. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Neurochemical and metabolic effects of acute and chronic alcohol in the human brain: Studies with positron emission tomography. [2018]

6. Netherlands 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. [2019]

7. Denmark 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. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Nonoxidative ethanol metabolism in humans-from biomarkers to bioactive lipids. [2023]

9. United States 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

In vivo research with stable isotopes in biochemistry, nutrition and clinical medicine: an overview. [2008]

11. England 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. [2021]