Improving Physical Function in Older Adults Using an Anti-inflammation Drug: The RIGHT Study

Inclusion Criteria:

• Persons aged ≥ 70 years at time of randomization

• Gait speed ≥ 0.44 m/sec to < 1.0 m/sec or BMI ≥ 28 kg/m2

• IL-6 level ≥ 2.0 pg/ml but < 30.0 pg/ml

• Self-reported difficulty walking ¼ mile or climbing 10 steps

• Self-reported ability to walk 400 meters (about 2-3 blocks), unassisted

• Self-reported vaccinations for COVID-19, Influenza and pneumococcal pneumonia up todate per current CDC guidelines

Exclusion Criteria:

• Advanced neurologic disorder such as dementia, Parkinson's disease, amytrophiclateral sclerosis, or multiple sclerosis that would impact the ability to improve onfunctional assessments

• Resident in a nursing home

• Severe hearing or vision loss that would impair participant's ability to completequestionnaires or follow oral instructions, and which may limit feasibility ofperforming functional assessments

• Acute infections (including but not limited to common cold virus, shingles virus,bronchitis, skin infection, urinary tract infection, tooth abscess) within 60 daysof randomization

• Chronic infection (including but not limited to):

• History of active TB or evidence of latent TB based on a positive PPD skintest, positive Quantiferon TB-Gold test, or a history of old or latent TB onchest x-ray

• History of Hepatitis B or Hepatitis C

• Previous diagnosis of Human Immunodeficiency Virus (HIV) or AcquiredImmunoDeficiency Syndrome (AIDS)

• Inflammatory or autoimmune disease (including but not limited to rheumatoidarthritis, lupus, or inflammatory bowel disease, such as ulcerative colitis orCrohn's disease)

• Immunization with a live/attenuated vaccine within 2 months prior to randomization (e.g., viral: measles vaccine, mumps vaccine, rubella vaccine, live attenuatedinfluenza vaccine, live attenuated chicken pox or shingles vaccine, smallpoxvaccine, oral polio vaccine (Sabin), rotavirus vaccine, and yellow fever vaccine.Bacterial: BCG vaccine, oral typhoid vaccine and epidemic typhus vaccine)

• Current use of chronic immune modulating medications such as corticosteroids,monoclonal antibodies, janus kinase inhibitors, calcineurin inhibitors, mTORinhibitors, IMDH inhibitors, or biologics

• Admitted for an overnight hospitalization in the last 6 months

• Open-chest heart surgery (including, but not limited to, coronary artery bypassgraft surgery or aortic valve surgery) in the past 6 months

• Anticipating major surgery (including, but not limited to, chest, abdomen, or jointsurgery) in the next 6 months

• Deep vein thrombosis or pulmonary embolus in the past 6 months

• Severe lung disease or heart disease that requires oxygen use anytime during the day (including, but not limited to, use only during activity, use only at night or useall day)

• Tobacco use (including cigarettes, cigar, pipe, or vaping) or inhaled cannabis inthe past 6 months

• Current consumption of > 14 alcoholic drinks per week

• History of substance abuse including cocaine, methamphetamine, opioids, ornarcotics; any use of cannabis

• Uncontrolled diabetes, noncompliant with treatment or fasting glucose > 250 mg/dL

• Cancer: Stage 1 cancer (including melanoma skin cancers) within the past 5 years,other than adequately treated (fully excised and recovered from surgery based on thejudgement of a study MD) basal and/or squamous cell skin cancer, or stage 2 or stage 3 cancer within 10 years, or any history of stage 4 (metastatic) cancer

• Inability to get a normal systolic blood pressure reading (between 100-180) at twoconsecutive visits prior to randomization (must be at least 1 day apart)

• ALT, AST, or Total Bilirubin > Upper Limit of Normal (ULN)

• Absolute Neutrophil Count outside normal range or < 1.5 x109/L

• White Blood Count outside normal range

• Platelet count outside normal range or < 125 x109/L

• Hemoglobin <10 g/dL

• Total Cholesterol > 300 mg/dL or Triglycerides > 400 mg/dL

• Dialysis treatment or chronic renal insufficiency defined as CKD-EPI eGFR < 25ml/min/(1.73) m2

• History of diverticular disease or GI perforation

• History of severe allergic or anaphylactic reactions to human, humanized, or murinemonoclonal antibodies

• Current use of Warfarin (Coumadin, Jantoven)

• Unable or unwilling to provide informed consent

• Current participation in another interventional study (including trials of exercise,diet, or investigational drugs)

• A psychiatric disorder that is impairing ability to consent or comply withrequirements of the trial

• Residence or travel outside of the study area for more than one month during thestudy or planning to move out of the area in the next six months.

• Other conditions which at the discretion of a study physician investigator whichwould make participation unsafe or inappropriate (logistic, behavioral, medical)