Antioxidant Replacement Therapy in Patients With Alcohol Abuse
Condition: Alcohol Abuse
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 2

Summary: 
      Alcohol is one of the most commonly abused drugs in the world. Up to 40% of medical and
      surgical patients have alcohol related problems, and alcohol use accounts for more than 10%
      of U.S. health care costs. In the intensive care unit (ICU), patients with a history of
      alcohol abuse are common where their rates of mortality and ICU-related morbidity are
      significantly higher when compared to patients without a history of alcohol abuse. Though ICU
      patients are a heterogeneous group, Acute Respiratory Distress Syndrome (ARDS), a devastating
      form of acute lung injury, is one of the more frequent diagnoses among these critically ill
      patients.

      In 1996, we made the novel observation that a prior history of chronic alcohol abuse is
      associated with an increased incidence and severity of ARDS in critically ill patients. In
      our epidemiological studies of over 570 critically ill patients, 50% of all patients with
      ARDS have a significant history of chronic alcohol abuse. Since ARDS affects approximately
      150,000 patients per year in the United States, and mortality is 40-50% even in previously
      healthy individuals, alcohol-related ARDS is an enormous national health care problem. We
      estimate that between 15,000 and 25,000 deaths per year in the United States are associated
      with alcohol-related ARDS, a number consistent with or even exceeding the number of deaths
      due to many other alcohol-related diseases such as cirrhosis of the liver and alcohol-related
      traffic accidents. Further investigations of the association between chronic alcohol abuse
      and ARDS are needed to develop therapies that improve morbidity and mortality in this
      important patient population.

      The clinical syndrome of ARDS is defined as refractory hypoxemia with bilateral infiltrates
      on chest radiograph in the absence of left atrial hypertension. Pathophysiologically, ARDS is
      characterized by diffuse alveolar damage, increased pulmonary alveolar-capillary
      permeability, and the subsequent accumulation of extravascular lung water. In animal models
      of chronic alcohol abuse, we showed that chronic ethanol ingestion causes chronic oxidative
      stress, depletes lung glutathione, impairs alveolar-capillary barrier function, and
      exaggerates endotoxin-mediated acute lung injury. Ethanol-mediated disruption of the
      alveolar-capillary barrier, and the associated susceptibility to acute edematous injury, is
      modified by glutathione (GSH) replacement therapy in animal models.

      Responding to NIH emphasis on studies of the mechanisms of disease and evaluation of
      therapies in human subjects, our group has initiated translational studies that expand our
      basic observations of the effects of chronic alcohol abuse on ARDS to the clinical setting.
      We recently reported that lung epithelial lining fluid from individuals with a prior history
      of chronic alcohol abuse is deficient in GSH, an essential antioxidant. The translational
      experiments outlined in this proposal will identify alterations in the structure and function
      of the lung in individuals with a history of chronic alcohol abuse and test a novel medical
      therapy that may ultimately decrease the morbidity and mortality for 50,000-75,000 ARDS
      patients with a prior history of chronic alcohol abuse per year in the United States.

      We propose the following hypothesis that antioxidant deficiency is a cause of abnormal
      alveolar-capillary barrier function in individuals with a history of chronic alcohol abuse,
      and oral anti-oxidant replacement therapy will correct the abnormality.

      If this hypothesis can be confirmed, this work would pave the way for testing antioxidant
      replacement as prophylaxis against acute lung injury in alcoholic patients at risk for the
      development of ARDS.

      Specific Aim: To determine the safety and efficacy of in vivo antioxidant replacement therapy
      on alveolar-capillary barrier function in individuals with a history of chronic alcohol
      abuse.
    


Intervention name(s): Protandim
Intervention type(s): Dietary Supplement
Intervention description(s): The dosage of Protandim will be 1350 mg per day given p.o. in two equally divided doses
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Supportive Care
Keywords: alcohol abuse; alveolar capillary permeability