Examination of Zinc, S-adenosylmethionine, and Combination Therapy Versus Placebo in Alcoholics
Condition: Alcoholism
MeSH terms: Alcoholism
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Bronchoscopy; Zinc sulfate 220 mg once daily; S-adenosylmethionine 400 mg twice daily
Intervention type(s): Procedure; Dietary Supplement; Dietary Supplement
Intervention description(s): Involves flexible fiberoptic bronchoscopy with standardized bronchoalveolar lavage (BAL) technique (isotonic saline in a sub-segment of the right middle lobe or lingula) using standard conscious sedation techniques.
Other intervention name(s): SAMe
Intervention MeSH terms: Zinc Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: alcoholism; lung health; pulmonary; macrophage; zinc; SAMe; S-adenosylmethionine; alveolar