NCT01899521: ExZACTO

Examination of Zinc, S-adenosylmethionine, and Combination Therapy Versus Placebo in Alcoholics

Completed NA Results posted Last updated 19 September 2024

What this trial tests

NA trial testing Bronchoscopy in Alcoholism in 113 participants. Completed in 31 July 2017.

Timeline

1 May 2013

Primary endpoint
31 July 2017

31 July 2017

Quick facts

Lead sponsor	VA Office of Research and Development
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	113
Start date	1 May 2013
Primary completion	31 July 2017
Estimated completion	31 July 2017
Sites	1 location across United States

Drugs / interventions tested

• Bronchoscopy
• Zinc sulfate 220 mg once daily
• S-adenosylmethionine 400 mg twice daily

Conditions studied

• Alcoholism — all drugs for Alcoholism →

Sponsor

VA Office of Research and Development — full company profile →

Who can join

Adults 18 to 60, any sex, with Alcoholism. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Primary Endpoint Primary · Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)

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.

Pre-treatment PI

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	13518	± 11677
Active Zinc and Placebo SAMe	15892	± 18961
Placebo Zinc and Active SAMe	10849	± 11087
Active Zinc and Active SAMe	15530	± 17627

Post-treatment PI

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	16704	± 15412
Active Zinc and Placebo SAMe	23850	± 47703
Placebo Zinc and Active SAMe	10734	± 9709
Active Zinc and Active SAMe	13955	± 14511

Secondary Endpoint Secondary · Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)

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.

Pre-treatment Intracellular Zinc

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	2816	± 2149
Active Zinc and Placebo SAMe	3410	± 2655
Placebo Zinc and Active SAMe	3883	± 2723
Active Zinc and Active SAMe	4174	± 3386

Post-treatment Intracellular Zinc

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	2710	± 1980
Active Zinc and Placebo SAMe	3510	± 2590
Placebo Zinc and Active SAMe	4327	± 3092
Active Zinc and Active SAMe	3103	± 2823

Secondary Endpoint Secondary · Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)

Improvement in redox potential in the alveolar space. Redox potential will be measured before and after treatment phase using lavage fluid and blood plasma.

Pre-treatment GSSG

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	33.0	± 30.5
Active Zinc and Placebo SAMe	28.0	± 29.2
Placebo Zinc and Active SAMe	21.6	± 25.3
Active Zinc and Active SAMe	28.5	± 30.6

Post-treatment GSSG

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	28.9	± 29.2
Active Zinc and Placebo SAMe	19.7	± 23.8
Placebo Zinc and Active SAMe	20.5	± 26.8
Active Zinc and Active SAMe	33.5	± 35.2

Secondary Endpoint Secondary · Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment)

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.

Pre-treatment Serum Zinc

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	79.5	± 18.5
Active Zinc and Placebo SAMe	76.9	± 12.0
Placebo Zinc and Active SAMe	78.5	± 12.1
Active Zinc and Active SAMe	75.0	± 11.0

Post-treatment Serum Zinc

Group	Value	95% CI
Placebo Zinc and Placebo SAMe	71.2	± 9.7
Active Zinc and Placebo SAMe	95.6	± 36.3
Placebo Zinc and Active SAMe	80.1	± 14.9
Active Zinc and Active SAMe	92.0	± 34.8

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Zinc and Placebo SAMe

Serious: 1/23 (4%)

Deaths: 0/23

Active Zinc and Placebo SAMe

Serious: 0/25 (0%)

Deaths: 0/25

Placebo Zinc and Active SAMe

Serious: 1/25 (4%)

Deaths: 0/25

Active Zinc and Active SAMe

Serious: 0/22 (0%)

Deaths: 0/22

Serious adverse events (2 terms)

Reaction	System	Placebo Zinc and Placebo S…	Active Zinc and Placebo SAMe	Placebo Zinc and Active SAMe	Active Zinc and Active SAMe
Subarachnoid hemorrhage	Vascular disorders	—	—	—	—
Alcohol withdrawal	Psychiatric disorders	—	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Placebo Zinc and Placebo S…	Active Zinc and Placebo SAMe	Placebo Zinc and Active SAMe	Active Zinc and Active SAMe
GI upset	Gastrointestinal disorders	—	—	—	—
Procedure-related	Injury, poisoning and procedural complications	—	—	—	—
Other	Investigations	—	—	—	—

Most-reported serious reactions: Subarachnoid hemorrhage, Alcohol withdrawal.

Data from ClinicalTrials.gov NCT01899521 adverse events section.

Sponsor's own description

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.

Publications & conference data

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

1. Alcohol and the Lung.
   Mehta AJ, Guidot DM. · · 2017 · cited 45× · PMID 28988576
2. Zinc as a Drug for Wilson's Disease, Non-Alcoholic Liver Disease and COVID-19-Related Liver Injury.
   Coni P, Pichiri G, Lachowicz JI, Ravarino A, et al · · 2021 · cited 17× · PMID 34771023 · DOI 10.3390/molecules26216614