NCT00936000

Double Blinded Placebo Controlled Trial of Protandim for Individuals With a History of Alcohol Abuse

Completed Phase 2 Last updated 5 February 2013

What this trial tests

Phase 2 trial testing Protandim in Alcohol Abuse in 38 participants. Completed in 1 September 2010.

Timeline

1 June 2009

Primary endpoint
1 September 2010

1 September 2010

Quick facts

Lead sponsor	University of Colorado, Denver
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	supportive care
Enrollment	38
Start date	1 June 2009
Primary completion	1 September 2010
Estimated completion	1 September 2010
Sites	1 location across United States

Drugs / interventions tested

• Protandim — full drug profile →

Conditions studied

• Alcohol Abuse — all drugs for Alcohol Abuse →

Sponsor

University of Colorado, Denver

Who can join

Adults 21 to 55, any sex, with Alcohol Abuse. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Improvement in alveolar capillary barrier function
  Time frame: within 7 days

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Alcohol-Induced Oxidative Stress and the Role of Antioxidants in Alcohol Use Disorder: A Systematic Review.
   Tsermpini EE, Plemenitaš Ilješ A, Dolžan V. · · 2022 · cited 98× · PMID 35883865 · DOI 10.3390/antiox11071374
2. Protandim does not influence alveolar epithelial permeability or intrapulmonary oxidative stress in human subjects with alcohol use disorders.
   Burnham EL, McCord JM, Bose S, Brown LA, et al · · 2012 · cited 17× · PMID 22268125 · DOI 10.1152/ajplung.00171.2011