Examination of Zinc, S-adenosylmethionine, and Combination Therapy Versus Placebo in Alcoholics
| Status: | Completed |
|---|---|
| Conditions: | Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 11/7/2018 |
| Start Date: | May 1, 2013 |
| End Date: | July 31, 2017 |
Alcohol Abuse, Oxidative Stress, and Zinc Deficiency in Lung Disease
This is a randomized, placebo controlled trial of dietary zinc and S-adenosylmethionine
(SAMe) in otherwise healthy alcoholic US Veterans. The primary goal is to determine if either
dietary zinc or S-adenosylmethionine (SAMe) can augment lung immune defenses in alcoholics
and thereby decrease the risk of lung injury and infection.
(SAMe) in otherwise healthy alcoholic US Veterans. The primary goal is to determine if either
dietary zinc or S-adenosylmethionine (SAMe) can augment lung immune defenses in alcoholics
and thereby decrease the risk of lung injury and infection.
Alcohol abuse is a major burden on society and even more of a problem in the Veteran
population. Chronic alcohol ingestion can have serious health consequences including
pneumonia and acute lung injury, which can occur suddenly and without warning even in
physically fit individuals without apparent signs of alcohol dependence. Therefore, it is
vital for the health of our Veterans and indeed the entire population to identify effective
treatments that can limit or even prevent these devastating consequences. The primary goal of
this clinical research project is to determine if dietary zinc or supplements of the
antioxidant S-adenosylmethionine (SAMe) can augment lung immune defenses in otherwise healthy
alcoholics and thereby decrease the risk of lung injury and infection. There is already
strong evidence from the investigators' experimental animal model that moderate daily alcohol
ingestion for as little as six weeks causes oxidative stress and zinc deficiency in the lung.
These derangements result insult in dysfunction of the alveolar macrophage, which is the
resident immune cell, and predisposes animals to the development of pneumonia. Importantly,
in this same animal model, the investigators found that adding either zinc or antioxidants to
the diet prevents these problems and preserves lung health even during daily alcohol
ingestion.
This project will translate basic findings in the animal model to the clinical setting and
determine whether or not zinc or SAMe supplements are effective in humans who pathologically
consume alcohol. This project will enroll Veterans seen at the Atlanta Veterans Hospital in
the Substance Abuse Treatment Program (SATP). Participants will be evaluated by undergoing a
procedure to obtain samples of fluid from their lungs, measure zinc levels, redox potential,
and assess how well their alveolar macrophages respond to bacteria (by determining phagocytic
capacity). After completion of the initial evaluation, the participants will be randomized to
receive standard treatment (placebo), zinc supplements, dietary SAMe, or the combination of
zinc and SAMe for 14 days. All subjects will be evaluated for two weeks as they undergo
treatment. At the end of this two week period, measurements of lung zinc, redox potential and
macrophage function will be repeated and compared between the two groups. The hypothesis is
that both dietary zinc and SAM supplements will improve the immune function of the alveolar
macrophage.
If this project is successful, it will lead to larger clinical trials to determine if either
dietary zinc and/or SAMe supplements can be effective even in the acute clinical setting and
improve outcomes in alcoholics who develop pneumonia or acute lung injury. Overall, both zinc
and SAMe supplements are safe and inexpensive to provide, allowing these potential treatments
to be easily implemented in the Veteran population as well as society in general. Given the
significant burden of unhealthy alcohol use, the investigators need ways to limit the
physical consequences of alcohol abuse while the investigators continue the efforts at public
education and addiction treatment.
population. Chronic alcohol ingestion can have serious health consequences including
pneumonia and acute lung injury, which can occur suddenly and without warning even in
physically fit individuals without apparent signs of alcohol dependence. Therefore, it is
vital for the health of our Veterans and indeed the entire population to identify effective
treatments that can limit or even prevent these devastating consequences. The primary goal of
this clinical research project is to determine if dietary zinc or supplements of the
antioxidant S-adenosylmethionine (SAMe) can augment lung immune defenses in otherwise healthy
alcoholics and thereby decrease the risk of lung injury and infection. There is already
strong evidence from the investigators' experimental animal model that moderate daily alcohol
ingestion for as little as six weeks causes oxidative stress and zinc deficiency in the lung.
These derangements result insult in dysfunction of the alveolar macrophage, which is the
resident immune cell, and predisposes animals to the development of pneumonia. Importantly,
in this same animal model, the investigators found that adding either zinc or antioxidants to
the diet prevents these problems and preserves lung health even during daily alcohol
ingestion.
This project will translate basic findings in the animal model to the clinical setting and
determine whether or not zinc or SAMe supplements are effective in humans who pathologically
consume alcohol. This project will enroll Veterans seen at the Atlanta Veterans Hospital in
the Substance Abuse Treatment Program (SATP). Participants will be evaluated by undergoing a
procedure to obtain samples of fluid from their lungs, measure zinc levels, redox potential,
and assess how well their alveolar macrophages respond to bacteria (by determining phagocytic
capacity). After completion of the initial evaluation, the participants will be randomized to
receive standard treatment (placebo), zinc supplements, dietary SAMe, or the combination of
zinc and SAMe for 14 days. All subjects will be evaluated for two weeks as they undergo
treatment. At the end of this two week period, measurements of lung zinc, redox potential and
macrophage function will be repeated and compared between the two groups. The hypothesis is
that both dietary zinc and SAM supplements will improve the immune function of the alveolar
macrophage.
If this project is successful, it will lead to larger clinical trials to determine if either
dietary zinc and/or SAMe supplements can be effective even in the acute clinical setting and
improve outcomes in alcoholics who develop pneumonia or acute lung injury. Overall, both zinc
and SAMe supplements are safe and inexpensive to provide, allowing these potential treatments
to be easily implemented in the Veteran population as well as society in general. Given the
significant burden of unhealthy alcohol use, the investigators need ways to limit the
physical consequences of alcohol abuse while the investigators continue the efforts at public
education and addiction treatment.
Inclusion Criteria:
- Age 18-60 years
- Active alcohol use disorder
Exclusion Criteria:
- Any active and uncontrolled medical problem(s)
- Known zinc deficiency
- Primary substance of abuse something other than alcohol
- Current abnormal chest x-ray
- HIV-positive
- Any disorder of blood coagulation
- Currently on medical treatment with anti-coagulants, including:
- warfarin
- heparin
- direct thrombin inhibitors
- anti-platelet agents (other than Aspirin)
- Daily use of vitamins or other nutritional supplements (unless taking as treatment for
alcohol use disorder)
- Renal impairment (GFR < 60)
- Active bipolar disorder
- Active Parkinson's disease
- Current pregnancy
- Contraindication to treatment with zinc or S-adenosylmethionine
- Inability to give informed consent (i.e., limited cognitive capacity)
- Non-English speaking
We found this trial at
1
site
Decatur, Georgia 30033
Principal Investigator: Ashish Mehta, MD
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