Inflammation Control For Elders: ICE Study

NCT02079948 | Withdrawn Phase 2 DMC

• 2 other identifiers: 1182013P30AG028740
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will be the first to test whether a selected anti-inflammatory agent, methotrexate, reduces inflammation in a human body, improve cognitive and physical function, and reduce pain levels in older adults at risk for functional decline, due to systemic inflammation.

Conditions

Inflammation; Aging

Keywords

Aging; Cognitive Function; Physical Function; Systematic Inflammation; Methotrexate; Pain Symptoms

Outcome Measures

Primary Outcomes (1)

• Markers of Systemic Inflammation

  To examine the effects of methotrexate on changes in markers of systemic inflammation (e.g., IL-6, CRP) and cellular inflammation (e.g., IL-6, TNF-α, and IL11β).

  6 Months

Secondary Outcomes (3)

• Physical Function

  6 Months

• Cognitive Performance

  6 Months

• Pain Symptoms

  6 Months

Study Arms (4)

Methotrexate + Folic Acid

ACTIVE COMPARATOR

Participants in the methotrexate condition will consume a dose of 15 mg/week of methotrexate during months 2 - 6. Participants will also consume 1 mg of folic acid/day for six days per week.

Procedure: Functional MRI Experimental Tasks; Procedure: Muscle Biopsy

Placebo + Folic Acid

PLACEBO COMPARATOR

Participants in the placebo condition will consume microcrystalline cellulose once per week. The number of capsules consumed on this day will match the number of capsules consumed by participants in the methotrexate condition. There are no active ingredients in the placebo capsules.

Procedure: Functional MRI Experimental Tasks; Procedure: Muscle Biopsy

Functional MRI Experimental Tasks

EXPERIMENTAL

15 participants will be randomly assigned to complete the fMRI visits at the baseline and 6 month.

Drug: Methotrexate + Folic Acid; Drug: Placebo + Folic Acid

Muscle Biopsy

EXPERIMENTAL

10 participants will be randomly assigned to complete the skeletal muscle tissue sample at the baseline and 6 month visits.

Drug: Methotrexate + Folic Acid; Drug: Placebo + Folic Acid

Interventions

Methotrexate + Folic Acid DRUG

Participants in the methotrexate + folic acid condition will have a * Blood draw at each monthly visit * Cognitive performance testing to assess memory performance * Physical function testing to assess walking speed and measure muscle endurance * Pain assessment testing to assess the presence and location of daily pain * Self-reported function and quality of life to measure disability and mobility limitations, and * Depression assessment testing to assess participants' level of depression.

Also known as: Trexall, Rheumatrex

Functional MRI Experimental Tasks; Muscle Biopsy

Placebo + Folic Acid DRUG

Participants in the placebo + folic acid condition will have a * Blood draw at each monthly visit * Cognitive performance testing to assess memory performance * Physical function testing to assess walking speed and measure muscle endurance * Pain assessment testing to assess the presence and location of daily pain * Self-reported function and quality of life to measure disability and mobility limitations, and * Depression assessment testing to assess participants' level of depression

Also known as: Microcrystalline Cellulose

Functional MRI Experimental Tasks; Muscle Biopsy

Functional MRI Experimental Tasks PROCEDURE

Participants who are randomly assigned to the fMRI scan wil receive their study drugs at the the Baseline fMRI visit. Participants who are randomly assigned to the fMRI will also attend complete their last visit at the 6 month period.

Also known as: - MRI, -Magnetic Resonance (MR), -Nuclear Magnetic Resonance (NMR) Imaging

Methotrexate + Folic Acid; Placebo + Folic Acid

Muscle Biopsy PROCEDURE

Participants who are randomly assigned to the muscle biopsy assessment of the study will receive their study drugs at the Baseline muscle biopsy visit. Participants who are randomly assigned to the muscle biopsy portion of the study will also complete their last visit at the 6 month period.

Also known as: -Biopsy, -Muscle Tissue Sample

Methotrexate + Folic Acid; Placebo + Folic Acid

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• years of age or over
• Blood Level of IL-6: \> 2.54 pg/mL
• Physical Activity: \< 120 minutes of moderate intensity physical activity per week
• Mild-to-moderate physical impairment: (SPPB \< 9)
• Blood Pressure: \< 160/90 mm Hg
• Willing and able to give informed consent

You may not qualify if:

• Significant underlying disease that is likely to limit participation and/or increase risk of interventions
• History or diagnosis of cardiovascular disease, myocardial infarction (heart attack), cerebrovascular accident, or unstable angina NYHA Class 3 or 4 congestive heart failure; aortic stenosis; cardiac arrest, use of a cardiac defibrillator, or uncontrolled angina within the past 6 months;
• History or diagnosis of severe lung disease within the past 6 months
• Known chronic pericardial effusion, pleural effusion, or ascites; chronic liver disease; myeloproliferative disorders in the past 5 years; Lymphoproliferative disease diagnosed and/or treated within the last five years; non-basal cell malignancy
• Prior history of chronic infectious disease, renal insufficiency, interstitial lung disease, pneumonitis, bronchiectasis, pulmonary fibrosis, or pulmonary disease
• Cognitive impairment and/or diagnosis of dementia
• Failure to provide informed consent
• Current usage of methotrexate therapy
• Consume alcohol and refuses to reduce alcohol use to 3 or fewer drinks per week during the study
• History of drug or alcohol abuse or excessive alcohol use within past six months
• Abnormal laboratory values
• White blood cell count \< 4,000/ul, hematocrit \< 32%, or platelet count \< 75,000/ul
• Liver transaminase levels (AST or ALT) \> upper limit of normal (ULN) or albumin \< the lower limit of normal (LLN)
• Creatinine clearance \< 40 ml/min as estimated with the Cockroft-Gault equation
• Hypercalcemia (calcium \> 10.4 mg/dL), hypocalcemia (calcium \< 8.6 mg/dL), renal insufficiency (estimated glomerular filtration rate (eGFR) \< 50 ml/min)

Sponsors & Collaborators

• University of Florida: lead
• National Institute on Aging (NIA): collaborator

MeSH Terms

Conditions

Inflammation; Pain

Interventions

Methotrexate; Folic Acid; microcrystalline cellulose; Magnetic Resonance Spectroscopy; X-Rays; Biopsy

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Stephen Anton, PhD

  University of Florida, Institute on Aging

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2014
• First Posted: March 6, 2014
• Study Start: February 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: January 11, 2022

Record last verified: 2022-01