Zinc Intervention in Elderly for Prevention of Pneumonia (ZIPP)

Pneumonia is a major public health problem for the elderly and is one of the leading causes of hospitalization and death for this population, particularly for elderly nursing home residents. This planning grants seeks to establish a safe and effective dose of zinc supplementation with the goal to conduct a larger randomized clinical trial to study the effect of zinc supplementation in nursing home elderly with low serum zinc levels on the risk, antibiotic use, and duration of sick days with pneumonia. This project has significant potential to positively impact the health and quality of life in the elderly and to reduce the economic costs associated with their care.

Study Overview

• Status: Completed
• Conditions: Zinc Deficiency
• Intervention / Treatment: Drug: Zinc gluconate

Detailed Description

Pneumonia (PNA) is a leading cause of death and a major public health problem in the elderly, particularly for nursing home (NH) residents. Thus, there is an urgent need for effective strategies to prevent PNA in elderly. An important predisposing factor that may account for the higher incidence of PNA in older adults is the age-associated decline in T cell function. Importantly, there are remarkable similarities between Zn deficiency and age-induced changes in T cells. The investigators have shown that 29% of NH residents have low serum Zn levels, which was associated with higher incidence and duration of PNA, and antibiotic use. Although our preliminary data strongly suggest that low serum Zn is an independent risk factor for PNA in the elderly, a controlled clinical trial is critically needed to determine the efficacy of Zn supplementation in PNA prevention in this population. The objective of the larger clinical trial that will pursue the studies proposed in this R34 is to determine the effects of Zn supplementation on PNA outcomes in NH elderly and to understand their mechanistic basis. The central hypothesis is that improving Zn status in NH elderly with low serum Zn will reduce the incidence and duration of PNA, and the frequency of antibiotic use, and that the effect of Zn is mediated mainly through the improvement of T cell function. The rationale for conducting the proposed clinical trial is to determine the value of Zn supplementation as an inexpensive, easily implemented intervention that would aid in the prevention of PNA in the elderly. In a previous study NH elderly with low serum Zn levels, who were supplemented with 30 mg/d of Zn and ½ RDA of essential micronutrients showed, on average, significantly improved serum Zn levels. However, only 58% of participant became serum Zn adequate. The investigators therefore hypothesize that either a higher dose or a longer duration of supplementation is required to achieve adequate serum Zn levels in all Zn deficient elderly. The rationale for conducting the proposed pilot study is to determine the most effective yet safe dose for Zn supplementation in NH residents to be used in the larger clinical trial described above. The Specific Aim of the proposed two-year, pilot study is to establish the optimal dose of supplemental Zn to achieve adequate Zn status, and improved T cell function in Zn deficient elderly. This will be accomplished by conducting a randomized, placebo-controlled, double-blind clinical trial to test the efficacy of supplementation with 30 or 60 mg/d of Zn for 12 months on serum and T cell Zn levels, T cell function, and adverse events. The findings of this proposal are scientifically essential, yet sufficient, to allow us to make definitive decisions that inform the final design of our planned clinical trial, which aims to establish the value of Zn supplementation as an inexpensive, easily implemented intervention that would aid in the prevention of PNA, limit the duration of PNA, and consequently reduce the need for antimicrobial therapy in the elderly.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Jean Mayer USDA Human Nutrition Research Center on Aging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Elderly males and females (≥65 years)
2. >6 mo life expectancy, as judged by physician
3. Willing to be randomized into study groups
4. Able to swallow pills
5. Not currently on antibiotics
6. If consuming RDA levels of supplement, willing to replace with our control supplement
7. Calcium, vitamin D, and iron supplements permitted
8. Willing to receive influenza vaccine
9. BMI>18 kg/m2 and albumin >3.0 g/dL

Exclusion Criteria:

1. Anticipated transfer or discharge within 3 months of enrollment
2. Bed- or room-bound continuously for previous 3 months
3. Presence of lung neoplastic diseases or other active neoplastic diseases requiring chemotherapy and/or immunosuppressive drugs (including ≤10 mg/day prednisone)
4. Naso-gastric or other tube feeding
5. Long-term (≥30 days) IV or urethral catheters
6. Presence of tracheostomy or chronically ventilator-dependent
7. Chronic prophylactic antibiotic treatment or long term antibiotics
8. Those with PEM defined as albumin <3.0 g/dl and BMI <18kg/m2, 10
9. Consumption of supplements containing more than the RDA level of nutrients known to affect the immune response, i.e. vitamins E, C, B6, selenium, Zn, or beta-carotene
10. Diagnosis of PNA or other infection at baseline will not exclude a subject, but will postpone enrollment to 4 wks after PNA symptoms have cleared.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; ½ RDA of micronutrients including 5 mg/d Zn	Drug: Zinc gluconate; 30 and 60 mg/d of zinc gluconate
Experimental: Zinc 30 mg; ½ RDA of micronutrients including 30 mg/d Zn	Drug: Zinc gluconate; 30 and 60 mg/d of zinc gluconate
Experimental: Zinc 60 mg; ½ RDA of micronutrients including 60 mg/d Zn	Drug: Zinc gluconate; 30 and 60 mg/d of zinc gluconate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Zn levels	serum and intracellular Zn levels	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T cell profile	Total T cells, helper T cells, and cytotoxic T cells in PBMC will be determined by measuring populations of CD3, CD4, and CD8 positive cells, respectively, using flow cytometry.	12 months
T cell proliferation	PBMC will be incubated in the presence of T cell mitogens Con A or PHA, or antibodies against CD3 (T cell receptor) and CD28 (T cell co-receptor) for 72 h. Cultures will be pulsed with 0.5 μCi [3H]-thymidine (Perkin Elmer) during the last 4 h of incubation and then harvested onto glass-fiber mats (Wallac) with a Perkin Elmer cell harvester (Perkin Elmer). Cell proliferation will be assessed by the amount of [3H]-thymidine incorporated into the DNA as determined with the liquid-scintillation counting with a Micro Beta 2 MicroPlate counter (Perkin Elmer).	12 months
side effects	number of side effects will be recorded	12 months

Collaborators and Investigators

• Sponsor: Tufts University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2022
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: September 1, 2022
• First Posted (Actual): September 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 30, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: R34HL153277 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No