An interventional study of Bronchoscopy and Zinc sulfate 220 mg once daily in Alcoholism, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2024-09-19.
Sponsored by VA Office of Research and Development · Not applicable, Interventional, and Treatment
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.
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.
1,606 studies on the registry are indexed under Alcoholism; 328 are open to participants now.
This study's enrollment of 113 is above the median of 87 across 1,371 interventional studies indexed under Alcoholism.
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Of its 206 completed or terminated interventional studies of FDA-regulated products, 180 (87%) have results posted.
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Exclusion Criteria:
Currently on medical treatment with anti-coagulants, including:
Placebo tablet of zinc sulfate once daily and placebo tablet of s-adenosylmethionine twice daily
Procedure: Bronchoscopy
Zinc sulfate 220 mg once daily and placebo tablet of s-adenosylmethionine twice daily
Procedure: Bronchoscopy · Dietary Supplement: Zinc sulfate 220 mg once daily
Placebo tablet of zinc sulfate once daily and s-adenosylmethionine 400 mg twice daily
Procedure: Bronchoscopy · Dietary Supplement: S-adenosylmethionine 400 mg twice daily
Zinc sulfate 220 mg once daily and s-adenosylmethionine 400 mg twice daily
Procedure: Bronchoscopy · Dietary Supplement: Zinc sulfate 220 mg once daily · Dietary Supplement: S-adenosylmethionine 400 mg twice daily
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.
Also known as: SAMe
Primary Endpoint
Improvement in alveolar macrophage phagocytic index. Phagocytic index will be measured before and after treatment phase. Phagocytic index is calculated using isolated alveolar macrophages from the bronchoscopy procedure such that phagocytic index = (total number of engulfed cells/total number of counted macrophages) x (number of macrophages containing engulfed cells/total number of counted macrophages) x 100.
Time frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)
Secondary Endpoint
Improvement in alveolar macrophage intracellular zinc. Intracellular zinc will be measured before and after treatment phase using isolated alveolar macrophages. The units of measure are relative fluorescence units/cell (RFU/cell) and measured using confocal microscopy techniques.
Time frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)
Secondary Endpoint
Improvement in redox potential in the alveolar space. Redox potential will be measured before and after treatment phase using lavage fluid and blood plasma.
Time frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)
Secondary Endpoint
Improvement in alveolar macrophage granulocyte macrophage - colony stimulating factor (GM-CSF) receptor expression. GM-CSF receptor expression will be measured before and after treatment phase using isolated alveolar macrophages. The units of measure are relative fluorescence units/cell (RFU/cell) and measured using confocal microscopy techniques. Both alpha- and beta-subunits of the receptor will be measured.
Time frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)
Secondary Endpoint
Improvement in serum zinc level. Serum zinc will be measured before and after treatment phase by collecting blood plasma. The units of measure are mcg/dl.
Time frame: Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)
| Milestone | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe |
|---|---|---|---|---|
| Started | 23 | 25 | 25 | 22 |
| Completed | 18 | 24 | 24 | 20 |
| Not completed | 5 | 1 | 1 | 2 |
Improvement in alveolar macrophage phagocytic index. Phagocytic index will be measured before and after treatment phase. Phagocytic index is calculated using isolated alveolar macrophages from the bronchoscopy procedure such that phagocytic index = (total number of engulfed cells/total number of counted macrophages) x (number of macrophages containing engulfed cells/total number of counted macrophages) x 100.
| Phagocytic Index (PI) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe |
|---|---|---|---|---|
| Pre-treatment PI | 13518 ± 11677 | 15892 ± 18961 | 10849 ± 11087 | 15530 ± 17627 |
| Post-treatment PI | 16704 ± 15412 | 23850 ± 47703 | 10734 ± 9709 | 13955 ± 14511 |
Improvement in alveolar macrophage intracellular zinc. Intracellular zinc will be measured before and after treatment phase using isolated alveolar macrophages. The units of measure are relative fluorescence units/cell (RFU/cell) and measured using confocal microscopy techniques.
| RFU/cell | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe |
|---|---|---|---|---|
| Pre-treatment Intracellular Zinc | 2816 ± 2149 | 3410 ± 2655 | 3883 ± 2723 | 4174 ± 3386 |
| Post-treatment Intracellular Zinc | 2710 ± 1980 | 3510 ± 2590 | 4327 ± 3092 | 3103 ± 2823 |
Improvement in redox potential in the alveolar space. Redox potential will be measured before and after treatment phase using lavage fluid and blood plasma.
| GSSG percentage (measure of oxidation) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe |
|---|---|---|---|---|
| Pre-treatment GSSG | 33.0 ± 30.5 | 28.0 ± 29.2 | 21.6 ± 25.3 | 28.5 ± 30.6 |
| Post-treatment GSSG | 28.9 ± 29.2 | 19.7 ± 23.8 | 20.5 ± 26.8 | 33.5 ± 35.2 |
Improvement in alveolar macrophage granulocyte macrophage - colony stimulating factor (GM-CSF) receptor expression. GM-CSF receptor expression will be measured before and after treatment phase using isolated alveolar macrophages. The units of measure are relative fluorescence units/cell (RFU/cell) and measured using confocal microscopy techniques. Both alpha- and beta-subunits of the receptor will be measured.
No measurements were reported for this outcome.
Improvement in serum zinc level. Serum zinc will be measured before and after treatment phase by collecting blood plasma. The units of measure are mcg/dl.
| mcg/dl | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe |
|---|---|---|---|---|
| Pre-treatment Serum Zinc | 79.5 ± 18.5 | 76.9 ± 12.0 | 78.5 ± 12.1 | 75.0 ± 11.0 |
| Post-treatment Serum Zinc | 71.2 ± 9.7 | 95.6 ± 36.3 | 80.1 ± 14.9 | 92.0 ± 34.8 |
Collected over Up to one month following the final bronchoscopy procedure, a total of about two months. Subjects were assessed while they were enrolled and taking study medications and completed all study procedures after the second bronchoscopy. They were contacted from day following procedure up to a total 4 weeks after the final procedure date to assess for any additional adverse events. The total time period is about two months, including time during the study and after the final bronchoscopy procedure.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo Zinc and Placebo SAMe | 0/23 (0%) | 1/23 (4.3%) | 17/23 (73.9%) |
| Active Zinc and Placebo SAMe | 0/25 (0%) | 0/25 (0%) | 21/25 (84%) |
| Placebo Zinc and Active SAMe | 0/25 (0%) | 1/25 (4%) | 16/25 (64%) |
| Active Zinc and Active SAMe | 0/22 (0%) | 0/22 (0%) | 16/22 (72.7%) |
| Event | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe |
|---|---|---|---|---|
| Subarachnoid hemorrhageVascular disorders | 1/23 | 0/25 | 0/25 | 0/22 |
| Alcohol withdrawalPsychiatric disorders | 0/23 | 0/25 | 1/25 | 0/22 |
| Event | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe |
|---|---|---|---|---|
| GI upsetGastrointestinal disorders | 5/23 | 8/25 | 7/25 | 11/22 |
| Procedure-relatedInjury, poisoning and procedural complications | 8/23 | 9/25 | 8/25 | 6/22 |
| OtherInvestigations | 6/23 | 9/25 | 8/25 | 5/22 |
| Age, Categorical(Participants) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe | Total |
|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 23 | 25 | 25 | 22 | 95 |
| >=65 years | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe | Total |
|---|---|---|---|---|---|
| Median | 46 (28 to 60) | 47 (28 to 58) | 47 (29 to 60) | 51 (27 to 60) | 48 (27 to 60) |
| Sex: Female, Male(Participants) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe | Total |
|---|---|---|---|---|---|
| Female | 2 | 4 | 5 | 4 | 15 |
| Male | 21 | 21 | 20 | 18 | 80 |
| Ethnicity (NIH/OMB)(Participants) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 1 | 1 | 3 |
| Not Hispanic or Latino | 22 | 25 | 24 | 21 | 92 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 1 | 1 |
| Asian | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 17 | 20 | 21 | 19 | 77 |
| White | 4 | 2 | 2 | 2 | 10 |
| More than one race | 2 | 3 | 2 | 0 | 7 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe | Total |
|---|---|---|---|---|---|
| United States | 23 | 25 | 25 | 22 | 95 |
| Smoking Status(Participants) | Placebo Zinc and Placebo SAMe | Active Zinc and Placebo SAMe | Placebo Zinc and Active SAMe | Active Zinc and Active SAMe | Total |
|---|---|---|---|---|---|
| Smoker | 14 | 15 | 15 | 14 | 58 |
| Non-smoker | 9 | 10 | 10 | 8 | 37 |
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