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

Sponsor
Anne B. Newman (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05727384
Collaborator
CSL Behring (Industry)
60
1
2
24
2.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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. We 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 ≥ 2.5 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), tumor necrosis factor (TNF-alpha), other inflammatory markers, and changes in gene expression in circulating white blood cells

  • 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 ≥ 2.5 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, and immune function

  • To determine the safety and tolerability of clazakizumab 5 mg/month

This study will enroll 60 community living men and women 70 years of age and older who have mildly elevated IL-6 at baseline (≥ 2.5 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, 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 testing. Height, weight and pulse will be measured. Participants will complete questionnaire to assess 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 last injection.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Reducing Inflammation for Greater Health Trial: The RIGHT Study
Anticipated Study Start Date :
Mar 1, 2023
Anticipated Primary Completion Date :
Sep 1, 2024
Anticipated Study Completion Date :
Mar 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Clazakizumab

Participants received Clazakizumab 5 mg as a subcutaneous injection every 4 weeks for 24 weeks

Drug: Clazakizumab
5 mg, subcutaneous injection, every 4 weeks for 24 weeks

Placebo Comparator: Placebo

Participants received Clazakizumab placebo as a 5 mg subcutaneous injection every 4 weeks for 24 weeks

Drug: Placebo
5 mg, subcutaneous injection, every 4 weeks for 24 weeks

Outcome Measures

Primary Outcome Measures

  1. Mean Change in Speed of Walking 400 Meters from Baseline to 24 Weeks [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)]

    Assess effect of Clazakizumab versus placebo on speed of walking 400 meters (meters/second) from baseline to 24 weeks

Secondary Outcome Measures

  1. Mean Change in Oxygen Consumption While Walking from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess effect of Clazakizumab versus placebo on change of oxygen consumption (VO2 measured as ml/kg/min) with fixed speed walking on treadmill from baseline to 24 weeks

  2. Mean Change in Physical Function using the Short Physical Performance Battery Score (SPPB) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess effect of Clazakizumab versus placebo on change in SPPB score (0-12 points) from baseline to 24 weeks

  3. Mean Change in Muscle (Grip) Strength from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in muscle grip strength (kg) from baseline to 24 weeks

  4. Mean Change in Fatigue Level using the Pittsburgh Fatigability Score (PFS) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in PFS (physical subscale, 0-50) from baseline to 24 weeks

  5. Mean Change in Vascular Stiffness using Aortic Pulse Wave Velocity (APWV) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in APWV (cm/sec) from baseline to 24 weeks

  6. Mean Change in Cognitive Function using the Montreal Cognitive Assessment (MoCA) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in the MoCA score (0-30) from baseline to 24 weeks

  7. Mean Change in Cognitive Function using the California Verbal Learning Test (CVLT) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in the number correct for short word recall and long word recall, and the number of word intrusions/repititions using the CVLT from baseline to 24 weeks

  8. Mean Change in Cognitive Function using the Digit Symbol Substitution Test (DSST) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in the number correct on the DSST from baseline to 24 weeks

  9. Mean Change in Cognitive Function using the Trails Making Test A and B (Trails A and B) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in the time to complete (seconds) Trails A and B from baseline to 24 weeks

  10. Mean Change in Inflammatory Biomarker Free Interleukin 6 (IL-6) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on IL-6 (pg/mL) from Baseline to 24 weeks

  11. Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on CRP (mg/dL) from Baseline to 24 weeks

  12. Assess Safety and Tolerability of Clazakizumab by Monitoring Adverse Events (AEs) and Serious Adverse Events (SAEs) From Baseline to 44 Weeks [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]

    Assess the number of study participants reporting AEs and SAEs following the drug injection visits, at the final research assessment visit (24 weeks after baseline), and every 4 weeks for 20 weeks after the final research assessment visit

  13. Assess Safety and Tolerability of Clazakizumab by Monitoring Safety Laboratory Values From Baseline to 24 Weeks [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)]

    Compare the percent of participants (Clazakizumab versus placebo) with safety laboratory values for total white blood cell count, absolute neutrophil count, platelet count, liver function (alanine aminotransferase, aspartate aminotransferase and bilirubin, and lipids (total, HDL, and LDL cholesterol and triglycerides) outside of the normal range (as specified in the study protocol) to safely administer the study drug following the drug injection visits, and at the final research assessment visit (24 weeks after baseline).

  14. Assess Tolerability of Clazakizumab by Monitoring Adherence to Drug Administration From Baseline to 20 Weeks [Assessed at the time of the drug injection visits from baseline (randomization/first injection) through drug visits 2-6.]

    Tolerability will be assessed as adherence to the protocol expressed as a percentage of doses received and percentage of drug dosing visits attended in those receiving Clazakizumab versus placebo assessed following each drug injection visit (randomization/first drug injection visit and drug visits 2-6) line).

Other Outcome Measures

  1. Mean Change in Physical Activity Level using the Community Health Activities Model Program for Seniors (CHAMPS) Questionnaire from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change estimated kilocalories/kg/week and hours of moderate activity per week assessed by the CHAMPS from baseline to 24 weeks

  2. Mean Change in Physical Activity Level as Assessed by Actigraphy from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess effect of Clazakizumab versus placebo on change in mean time engaged in moderate to vigorous physical activity (MVPA) in minutes/week measured with actigraphy from baseline to 24 weeks

  3. Mean Change in Quality of Life using the Short Form 36 (SF-36) Health Survey from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in the SF-36 score (0-100) from baseline to 24 weeks

  4. Mean Change in Depression/Depressive Symptomatology using the Center for Epidemiologi Studies Depression Scale (CES-D) Short Form from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change CES-D score (0-30) from baseline to 24 weeks

  5. Mean Change in Sleep-Related Impairment using the Patient-Reported Outcomes Measurement Information System (PROMIS) from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in PROMIS sleep-related impairment t-score score (standardized score of 50, standard deviation of 10) from baseline to 24 weeks

  6. Mean Change in Disability using the Physical Subscale of Short Form 36 (SF-36) Health Survey from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in disability using the physical subscale of the SF-36 score (0-50) from baseline to 24 weeks

  7. Change in Frequency and Counts of Immune B and T Cell Subsets from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in the frequency (percent) and counts (cells/microliter) of immune cell subsets (T cells, B cells, other) using flow cytometry from Baseline to 24 weeks

  8. Change in Frequency and Counts of Memory B Cell Subsets from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in the frequency (percent) and counts (cells/microliter) of memory B cell subsets measured by flow cytometry from Baseline to 24 weeks

  9. Change in CD-8 T Cell Function from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on change in CD-8 T cell function in response to ex vivo stimulation measured by flow cytometry from Baseline to 24 weeks

  10. Mean Change in Inflammatory Cytokines using a 36-Plex Kit from Baseline to 24 Weeks [From baseline (randomization/first drug injection visit) to the final research assessment visit (24 weeks after baseline)]

    Assess the effect of Clazakizumab versus placebo on 36 cytokines (pg/mL) included in the Myriad V-PLEX Plus Human Cytokine 36-Plex kit from Baseline to 24 weeks

Eligibility Criteria

Criteria

Ages Eligible for Study:
70 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • Persons aged ≥ 70 years at time of randomization

  • Gait speed ≥ 0.44 m/sec to < 1.0 m/sec

  • IL-6 level ≥ 2.5 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, follow oral instructions, and which may limit feasibility of 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

  • Self-reported uncontrolled diabetes or fasting glucose > 200 mg/dL

  • Cancer: Stage 1 cancer (including melanoma and non-melanoma skin cancers) within the past 5 years, 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 outside normal sex-specific range

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

  • Dialysis treatment or chronic renal insufficiency defined as MDRD eGFR < 45 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 the site PI which would make participation unsafe or inappropriate (logistic, behavioral, medical)

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Pittsburgh, Health Studies Research Center Pittsburgh Pennsylvania United States 15260

Sponsors and Collaborators

  • Anne B. Newman
  • CSL Behring

Investigators

  • Principal Investigator: Anne B. Newman, MD, MPH, University of Pittsburgh

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Anne B. Newman, Professor, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT05727384
Other Study ID Numbers:
  • STUDY19030225
First Posted:
Feb 14, 2023
Last Update Posted:
Feb 14, 2023
Last Verified:
Feb 1, 2023
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 14, 2023