Vaccination Efficacy With Metformin in Older Adults: A Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B
研究概览
简要总结
With aging the immune system gets weaker. This makes older adults more susceptible to influenza (flu). Vaccinations help to prevent infection from the flu virus, however the immune system of older adults do not respond as well to vaccines compared to young adults and thus, aren't as well protected from the complications from the flu. This research is being done to determine if Metformin, an FDA-approved diabetes medication, is effective at enhancing immune responses to flu vaccine in older men and women. Participants will be randomly assigned to either metformin or placebo treatment for a total of 22 weeks. Participants will be vaccinated with high-dose flu vaccine after 12 weeks of treatment. Immune responses will be evaluated throughout the study at 6 time points.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
Metformin and placebo tablets will be identical. Participants and researchers will not know treatment allocation.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women 65 years and older
- •Willingness to provide consent and participate in all aspects of the trial including randomization to the intervention group and receiving this year's flu vaccine
- •Received previous year's seasonal influenza vaccine
排除标准
- •History of severe renal impairment and/or eGFR ≤ 45 mL/min/1.73m2
- •Excessive alcohol use (more than 14 alcoholic drinks/week) or clinical/laboratory evidence of hepatic disease (via medical history and/or AST and/or ALT ≥ 3 times upper limit of normal at screening)
- •Acute or chronic metabolic acidosis (via medical history and/or low serum bicarbonate (< 22mEq/L), increased anion gap (> 10 mEq/L))
- •History of B12 deficiency within the last 10 years
- •Known type 2 diabetes or screening of prediabetic (HbA1c 5.7-6.4%) or diabetic (HbA1c ≥ 6.5%)
- •Currently taking metformin or other diabetes medications
- •Unwilling or unable (due to significant cognitive impairment) to provide informed consent
- •Terminal illness with life expectancy less than 12 months
- •Advanced neurological disorder (Parkinson's, ALS, MS, dementia)
- •Cancer or history of cancer in the past 2 years (excluding non-melanoma skin cancer) or any history of metastatic (stage 4) cancer
- •Significant co-morbid disease (severe chronic obstructive pulmonary disease, active rheumatologic diseases, chronic infection (HIV, tuberculosis), severe congestive heart failure (NYHA class 4), myocarditis, etc)
- •Myocardial infarction, stroke or hospitalization for heart failure in the last 12 months
- •Severe active psychiatric disorder (e.g. bipolar, schizophrenia)
- •Unable to complete physical performance testing due to medical conditions (at discretion of the PI)
- •Uncontrolled hypertension (systolic/diastolic blood pressure >150/90 mmHg)
- •Unintentional weight loss >10% in past 12 months
- •Allergy or history of adverse reaction to flu vaccine or any ingredients in flu vaccine, including eggs
- •History of Guillain-Barre syndrome following vaccination
- •Immunosuppressive disorders or taking immunosuppressive medications (including oral prednisone > 10mg/day)
- •Current participation in another interventional study
- •Refusal to receive flu vaccine
研究组 & 干预措施
Metformin Hydrochloride Extended Release Tablets
Patients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)).
干预措施: Metformin Hydrochloride Extended-Release Tablets (Drug)
Metformin Hydrochloride Extended Release Tablets
Patients will consume 3 tablets of 500mg metformin hydrochloride extended-release tablets daily (1500mg/day (after 3 week dose gradation)).
干预措施: Influenza Vaccine (Biological)
Placebo
Patients will consume 3 identical placebo tablets (after similar 3 week dose gradation).
干预措施: Influenza Vaccine (Biological)
结局指标
主要结局
Change in Cell-mediated Flu Vaccine Responses - inducible Granzyme B
时间窗: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)
Change in inducible Granzyme B levels in peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with live flu virus will be compared between the metformin and placebo group.
Change in Cell-mediated Flu Vaccine Responses - interferon(IFN)-γ/interleukin(IL)-10 ratio
时间窗: Prior to vaccination (week 12) and 5 weeks post vaccination (week 17)
Change in interferon(IFN)-γ/interleukin(IL)-10 ratio in culture supernatant of peripheral blood mononuclear cells (PBMCs) stimulated ex vivo with live flu virus will be compared between the metformin and placebo group.
次要结局
- Change in Influenza Antibody Titers(Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22))
- Change in T Cell Metabolic Phenotype(Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22))
- Change in T Cell Oxygen Consumption Rate(Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22))
- Change in Frailty Phenotype(Prior to treatment (week 0), prior to vaccination (week 12), and after vaccination (week 13, 17, and 22))
研究者
Jenna Bartley
Assistant Professor
UConn Health