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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00060773 | Other Identifier | Emory IRB | |
| IK2CX000643 | U.S. NIH Grant/Contract | View source |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo zinc and placebo SAMe | Placebo Comparator | Placebo tablet of zinc sulfate once daily and placebo tablet of s-adenosylmethionine twice daily |
|
| Active zinc and placebo SAMe | Active Comparator | Zinc sulfate 220 mg once daily and placebo tablet of s-adenosylmethionine twice daily |
|
| Placebo zinc and active SAMe | Active Comparator | Placebo tablet of zinc sulfate once daily and s-adenosylmethionine 400 mg twice daily |
|
| Active zinc and active SAMe | Active Comparator | Zinc sulfate 220 mg once daily and s-adenosylmethionine 400 mg twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bronchoscopy | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
Inclusion Criteria:
Exclusion Criteria:
Any active and uncontrolled medical problem(s)
Known zinc deficiency
Primary substance of abuse something other than alcohol
Current abnormal chest x-ray
HIV-positive
Any disorder of blood coagulation
Currently on medical treatment with anti-coagulants, including:
Daily use of vitamins or other nutritional supplements (unless taking as treatment for alcohol use disorder)
Renal impairment (GFR < 60)
Active bipolar disorder
Active Parkinson's disease
Current pregnancy
Contraindication to treatment with zinc or S-adenosylmethionine
Inability to give informed consent (i.e., limited cognitive capacity)
Non-English speaking
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| Name | Affiliation | Role |
|---|---|---|
| Ashish Mehta, MD | Atlanta VA Medical and Rehab Center, Decatur, GA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Atlanta VA Medical and Rehab Center, Decatur, GA | Decatur | Georgia | 30033 | United States |
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Participants are enrolled when they sign consent, however, only get randomized after completing first bronchoscopy procedure. Therefore, there were some participants who enrolled but never completed the procedure in order to be randomized into a group. This is the reason for the discrepancy in numbers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Zinc and Placebo SAMe | Placebo tablet of zinc sulfate once daily and placebo tablet of s-adenosylmethionine twice daily Bronchoscopy: 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. |
| FG001 | Active Zinc and Placebo SAMe | Zinc sulfate 220 mg once daily and placebo tablet of s-adenosylmethionine twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily |
| FG002 | Placebo Zinc and Active SAMe | Placebo tablet of zinc sulfate once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. S-adenosylmethionine 400 mg twice daily |
| FG003 | Active Zinc and Active SAMe | Zinc sulfate 220 mg once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily S-adenosylmethionine 400 mg twice daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo Zinc and Placebo SAMe | Placebo tablet of zinc sulfate once daily and placebo tablet of s-adenosylmethionine twice daily Bronchoscopy: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | Phagocytic Index (PI) | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo Zinc and Placebo SAMe | Placebo tablet of zinc sulfate once daily and placebo tablet of s-adenosylmethionine twice daily Bronchoscopy: 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Subarachnoid hemorrhage | Vascular disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| GI upset | Gastrointestinal disorders | Systematic Assessment | May be diarrhea, upset stomach, flatulence |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ashish Mehta | Atlanta VA Medical Center | 404-321-6111 | 207133 | Ashish.Mehta@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 21, 2017 | Aug 17, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D001999 | Bronchoscopy |
| D019287 | Zinc Sulfate |
| D012436 | S-Adenosylmethionine |
| ID | Term |
|---|---|
| D003948 | Diagnostic Techniques, Respiratory System |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D004724 | Endoscopy |
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| Zinc sulfate 220 mg once daily | Dietary Supplement |
|
| S-adenosylmethionine 400 mg twice daily | Dietary Supplement |
|
|
| 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. |
| 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. | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
| BG001 |
| Active Zinc and Placebo SAMe |
Zinc sulfate 220 mg once daily and placebo tablet of s-adenosylmethionine twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily |
| BG002 | Placebo Zinc and Active SAMe | Placebo tablet of zinc sulfate once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. S-adenosylmethionine 400 mg twice daily |
| BG003 | Active Zinc and Active SAMe | Zinc sulfate 220 mg once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily S-adenosylmethionine 400 mg twice daily |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Smoking Status | Count of Participants | Participants |
|
| OG001 | Active Zinc and Placebo SAMe | Zinc sulfate 220 mg once daily and placebo tablet of s-adenosylmethionine twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily |
| OG002 | Placebo Zinc and Active SAMe | Placebo tablet of zinc sulfate once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. S-adenosylmethionine 400 mg twice daily |
| OG003 | Active Zinc and Active SAMe | Zinc sulfate 220 mg once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily S-adenosylmethionine 400 mg twice daily |
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | RFU/cell | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
|
|
|
| Other Pre-specified | 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. | Posted | Mean | Standard Deviation | GSSG percentage (measure of oxidation) | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
|
|
|
| Other Pre-specified | 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. | The cells were not stained appropriately, so this secondary measure could not be completed because the results were not analyzable. | Posted | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
|
|
| Other Pre-specified | 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. | Posted | Mean | Standard Deviation | mcg/dl | Initial bronchoscopy to second bronchoscopy (Initial bronchoscopy performed prior to treatment and second bronchoscopy done 2-3 weeks after starting treatment) |
|
|
|
| 0 |
| 23 |
| 1 |
| 23 |
| 17 |
| 23 |
| EG001 | Active Zinc and Placebo SAMe | Zinc sulfate 220 mg once daily and placebo tablet of s-adenosylmethionine twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily | 0 | 25 | 0 | 25 | 21 | 25 |
| EG002 | Placebo Zinc and Active SAMe | Placebo tablet of zinc sulfate once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. S-adenosylmethionine 400 mg twice daily | 0 | 25 | 1 | 25 | 16 | 25 |
| EG003 | Active Zinc and Active SAMe | Zinc sulfate 220 mg once daily and s-adenosylmethionine 400 mg twice daily Bronchoscopy: 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. Zinc sulfate 220 mg once daily S-adenosylmethionine 400 mg twice daily | 0 | 22 | 0 | 22 | 16 | 22 |
| Alcohol withdrawal | Psychiatric disorders | Systematic Assessment |
|
|
| Procedure-related | Injury, poisoning and procedural complications | Systematic Assessment | Includes sore throat, chest soreness, cough |
|
| Other | Investigations | Systematic Assessment |
|
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| D003949 | Diagnostic Techniques, Surgical |
| D019060 | Minimally Invasive Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
| D013510 | Pulmonary Surgical Procedures |
| D019616 | Thoracic Surgical Procedures |
| D013431 | Sulfates |
| D013464 | Sulfuric Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D007287 | Inorganic Chemicals |
| D017967 | Zinc Compounds |
| D008715 | Methionine |
| D000603 | Amino Acids, Sulfur |
| D009930 | Organic Chemicals |
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| Post-treatment Intracellular Zinc |
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| Post-treatment GSSG |
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| Post-treatment Serum Zinc |
|