Clinical trial NCT05727384: Improving Physical Function in Older Adults Using an Anti-inflammation Drug: The RIGHT Study
Official title: Reducing Inflammation for Greater Health Trial: The RIGHT Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Inflammation
Frailty
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: CSL Behring
First posted: 2023-02-14
Enrollment: 60
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn about the effects of inflammation-lowering therapy on mobility and disability in older adults. The main questions it aims to answer are:

* Will therapy improve walking speed/pace?
* Will therapy improve levels of blood inflammation markers and other indicators of physical, cognitive and immune function?

Participants will be asked to receive injections of drug or placebo every 4 weeks for 24 weeks. They will also be asked to undergo testing that assesses physical function, thinking ability and brain health, breathing capacity, and blood vessel stiffness, and will have blood samples collected to measure immune function and to create a bank of samples for future testing. Comparisons will be made between those who receive drug and those who receive placebo.

Detailed description: The primary objective of this trial is to assess the impact of inflammation-lowering therapy with clazakizumab 5 mg/month on speed when walking 400 meters in older adults. The investigators hypothesize that participants treated with clazakizumab will see a larger 6-month improvement in their pace on a 400-meter walk than those provided placebo.

The aims of the study will be to:

* To test the effect of clazakizumab 5 mg/month for 6 months on walking speed during a 400- meter corridor walk in adults 70 years of age and older with baseline levels of IL-6 ≥ 2.0 pg/ml and \< 30 pg/ml
* To assess the effect of clazakizumab 5 mg/month on serum levels of free interleukin (IL-6), circulating C-reactive protein (CRP), and other inflammatory markers
* To assess the effect of clazakizumab 5 mg/month on oxygen utilization (VO2) during submaximal steady-state walking in adults 70 years of age and older with baseline levels of IL-6 ≥ 2.0 pg/ml and \< 30 pg/ml, physical function, physical activity, perceived fatigability (overall, by questionnaire and in association with preferred and fixed speed walking), cognition, body weight, blood pressure, vascular stiffness, endothelial function, kidney function and immune function
* To determine the safety and tolerability of clazakizumab 5 mg/month

This study will randomize 60 community living men and women 70 years of age and older who have mildly elevated IL-6 at baseline (≥ 2.0 pg/ml and \< 30.0 pg/ml). Interested individuals will undergo telephone and in-person screening visits (two) to determine eligibility (blood will be collected to measure IL-6, height and weight will be measured, a 4m walk test will be administered to determine gait speed, and a review of medical history, medications, a physical exam, and blood safety labs will be conducted to ensure safety to proceed/eligibility). Randomization to study drug or placebo will take place within 60 days of the first in-person screening visit and subsequent injections will take place every 4 weeks for 24 weeks. Participants will undergo physical function testing (400m walk, preferred \& fixed speed walk on a treadmill with oxygen consumption measurement, short physical performance battery, grip strength, actigraphy), cognitive testing, and aortic pulse wave velocity and endothelial function testing. Height, weight and pulse will be measured. Participants will complete questionnaires to assess demographics, physical activity level, fatigability, sleep quality, pain and depression. Blood will be collected/processed to measure immune function and stored frozen to create a biorepository of samples (serum, plasma, buffy coat) for future testing. Participants will be monitored for safety in between injection visits and for 5 months following the final in-person research visit.

Eligibility criteria: 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 to date per current CDC guidelines

Exclusion Criteria:

* Advanced neurologic disorder such as dementia, Parkinson's disease, amytrophic lateral sclerosis, or multiple sclerosis that would impact the ability to improve on functional assessments
* Resident in a nursing home
* Severe hearing or vision loss that would impair participant's ability to complete questionnaires or follow oral instructions, and which may limit feasibility of performing functional assessments
* Acute infections (including but not limited to common cold virus, shingles virus, bronchitis, skin infection, urinary tract infection, tooth abscess) within 60 days of randomization
* Chronic infection (including but not limited to):

  * History of active TB or evidence of latent TB based on a positive PPD skin test, positive Quantiferon TB-Gold test, or a history of old or latent TB on chest x-ray
  * History of Hepatitis B or Hepatitis C
  * Previous diagnosis of Human Immunodeficiency Virus (HIV) or Acquired ImmunoDeficiency Syndrome (AIDS)
* Inflammatory or autoimmune disease (including but not limited to rheumatoid arthritis, lupus, or inflammatory bowel disease, such as ulcerative colitis or Crohn's disease)
* Immunization with a live/attenuated vaccine within 2 months prior to randomization (e.g., viral: measles vaccine, mumps vaccine, rubella vaccine, live attenuated influenza vaccine, live attenuated chicken pox or shingles vaccine, smallpox vaccine, 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, mTOR inhibitors, 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 bypass graft surgery or aortic valve surgery) in the past 6 months
* Anticipating major surgery (including, but not limited to, chest, abdomen, or joint surgery) 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 use all day)
* Tobacco use (including cigarettes, cigar, pipe, or vaping) or inhaled cannabis in the past 6 months
* Current consumption of \> 14 alcoholic drinks per week
* History of substance abuse including cocaine, methamphetamine, opioids, or narcotics; 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 the judgement 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 two consecutive 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 \< 25 ml/min/(1.73) m2
* History of diverticular disease or GI perforation
* History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal 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 with requirements of the trial
* Residence or travel outside of the study area for more than one month during the study or planning to move out of the area in the next six months.
* Other conditions which at the discretion of a study physician investigator which would make participation unsafe or inappropriate (logistic, behavioral, medical)

Primary outcomes:
measure: Mean Change in Speed of Walking 400 Meters from Baseline to 24 Weeks
timeFrame: From enrollment (randomization/first drug injection visit) to the final research assessment visit (4 weeks after final drug injection visit or 24 weeks after enrollment)
Secondary outcomes:
measure: Mean Change in Oxygen Consumption While Walking from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Physical Function using the Short Physical Performance Battery (SPPB) Score from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Muscle (Grip) Strength from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Fatigue Level using the Pittsburgh Fatigability Score (PFS) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Vascular Stiffness using Aortic Pulse Wave Velocity (APWV) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Peripheral Microvascular Endothelial Function using Peripheral Arterial Tonometry (EndoPat) from baseline to 24 weeks.
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Cognitive Function using the Montreal Cognitive Assessment (MoCA) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Cognitive Function using the California Verbal Learning Test (CVLT) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Cognitive Function using the Digit Symbol Substitution Test (DSST) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Cognitive Function using the Trails Making Test A and B (Trails A and B) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Inflammatory Biomarker Interleukin 6 (IL-6) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Assess Safety and Tolerability of Clazakizumab by Monitoring Adverse Events (AEs) and Serious Adverse Events (SAEs) From Baseline to 44 Weeks
timeFrame: AEs and SAEs assessed weekly after randomization/first drug injection visit, one week after drug visits 2-6, at the final research assessment visit (24 weeks after baseline), and every 4 weeks for 20 weeks after the final research assessment visit
measure: Assess Safety and Tolerability of Clazakizumab by Monitoring Safety Laboratory Values From Baseline to 24 Weeks
timeFrame: assessed weekly after randomization/first drug injection visit, one week after drug visits 2-6, at the final research assessment visit (24 weeks after baseline)
measure: Assess Tolerability of Clazakizumab by Monitoring Adherence to Drug Administration From Baseline to 20 Weeks
timeFrame: Assessed at the time of the drug injection visits from baseline (randomization/first injection) through drug visits 2-6.
Other outcomes:
measure: Mean Change in Physical Activity Level using the Community Health Activities Model Program for Seniors (CHAMPS) Questionnaire from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Physical Activity Level as Assessed by Actigraphy from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Quality of Life using the Short Form 36 (SF-36) Health Survey from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Depression/Depressive Symptomatology using the Center for Epidemiologic Studies Depression Scale (CES-D) Short Form from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Sleep-Related Impairment using the Patient-Reported Outcomes Measurement Information System (PROMIS) from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Disability using the Physical Subscale of Short Form 36 (SF-36) Health Survey from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Change in Frequency of Immune B Cell, T Cell and Memory B Cell Subsets from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Change in Counts of Immune B Cell, T Cell and Memory B Cell Subsets from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Change in CD-8 T Cell Function from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
measure: Mean Change in Inflammatory Cytokines using a 36-Plex Kit from Baseline to 24 Weeks
timeFrame: From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Health Studies Research Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Anne B. Newman, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: