Clinical trial NCT05527899: Zinc Intervention in Elderly for Prevention of Pneumonia
Official title: Zinc Intervention in Elderly for Prevention of Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Zinc Deficiency
Lead sponsor: Tufts University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-09-06
Enrollment: 105
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: We will conduct a randomized, double-blind, placebo-controlled trial (RCT) in elderly NH residents with low serum Zn levels to evaluate the efficacy of 1 y of Zn supplementation (dose to be determined during R34 planning grant) in the prevention of PNA. Eligible subjects will be randomly assigned to one of two groups: both groups will receive a capsule containing ½ Recommended Dietary Allowance (RDA) of all the essential micronutrients, including 5 mg of elemental Zn; the Zn-supplemented group's capsule will contain an additional mg Zn gluconate (total equiv. of dose to be determined during R34 grant). Suppl. duration will be 12 mo to account for seasonal variations in the incidence of PNA.
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Zn levels
timeFrame: 12 months
Secondary outcomes:
measure: T cell profile
timeFrame: 12 months
measure: T cell proliferation
timeFrame: 12 months
measure: side effects
timeFrame: 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Jean Mayer USDA Human Nutrition Research Center on Aging
state: Massachusetts
Study officials:
References: