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InflammationPhase 2ICENCT02079948

Inflammation Control For Elders: ICE Study

A Phase 2 study testing Methotrexate + Folic Acid, Functional MRI Experimental Tasks and Muscle Biopsy in people with Inflammation and Aging, run by University of Florida.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
Conditions the study is for
Inflammation, Aging
What is being tested?
Methotrexate + Folic Acid, Functional MRI Experimental Tasks and Muscle Biopsy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Feb 2014to Sep 2014
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • 65 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

Who cannot join

  • 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
Show all 35Show fewer
  • 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)
  • Lives in a nursing home
  • Self-reported inability to walk one block without any type of assistive device
  • Chest pain or severe shortness of breath during the 400-meter walk test
  • Terminal illness with life expectancy less than 12 months, as determined by a physician
  • Medication exclusions (current use of anabolic medications [i.e., growth hormones or testosterone], antipsychotic agents, monoamine oxidase inhibitors, anticholinesterase inhibitors [i.e., Aricept], anticoagulant therapies [aspirin use is permitted], antibiotics for HIV or TB, or antibiotics for other uses currently or within the past two months)
  • Chronic use of oral steroid therapy or other immunosuppressive or biologic response modifiers
  • Requirement for use of drugs that alter folate metabolism or reduce tubular excretion or known allergies to antibiotics making avoidance of trimethoprim impossible
  • Planning to leave the area in the next year
  • Current smoker or less than 3 years quit
  • Men who plan to father children during the study period or who are unwilling to use effective forms of contraception
  • Women of child bearing potential
  • Other significant co-morbid disease (e.g., renal failure on hemodialysis)
  • Contraindications to fMRI (ex. cardiac pacemaker)
  • Participating in another clinical trial or has received an investigational product within 30 days prior to screening/enrollment
  • Any other condition that in the opinion of the principal investigator may compromise the participation in the study
  • Participants with contraindications to the muscle biopsy procedure can participate in the study but will not be asked to participate in the muscle biopsy procedure.
  • The temporary exclusions include the following:
  • Recent bacterial/viral infection (< 2 weeks)
  • Acute febrile illness in prior 2 months
  • Major surgery or hip/knee replacement in the past 6 months

About this study

Official title: Role of Methotrexate in Improving Physical Function in Older Adults With Elevated Levels of Inflammation

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.

Read the detailed description

If you decide to take part in this study, you will be randomly assigned (much like the flip of a coin) to receive either methotrexate or placebo. A placebo is a substance that looks like and is given in the same way as an experimental treatment but contains no medicine, for example [a sugar pill, an injection of saline (salt water)]. A placebo is used in research studies to show what effect a treatment has compared with taking nothing at all. If you are assigned to receive placebo, you will not receive the benefits of the methotrexate, if there are any, nor will you be exposed to its risks, which are described below under "What are the possible discomforts and risks?" Studies have shown, however, that about 1 in 3 persons who take a placebo do improve, if only for a short time. You and the physician and other persons doing the study will not know whether you are receiving placebo or methotrexate, but that information is available if it is needed. Also, you will have a 50% chance of receiving methotrexate and a 50% chance of receiving placebo.

Methotrexate lowers folate (vitamin B9) levels in the body, so when someone takes methotrexate, he/she needs to take folic acid. To make sure that methotrexate lowers levels of inflammation in the body and not folate, study participants in both groups will be given folic acid.

In the remainder of the description of what will be done, both the methotrexate and the placebo will be called "study treatment."

You will be given a study letter that describes the study. You will be asked to show this letter to your doctors and other medical specialists, so they know that you are participating in a study with study drugs.

You will be asked to take your study drugs every morning by mouth on an EMPTY STOMACH before breakfast. The study capsules containing methotrexate and the placebo will look the same.

Participants in the methotrexate group will slowly increase the amount of methotrexate they take in the first month up to the 15 mg/week. In the first week, participants will take 5 mg/week (i.e., 1 capsule on Day 7), in the second and third week they will take 10 mg/week (i.e., 2 capsules on Day 7), and in the fourth week they will take 15 mg/week (i.e., 3 capsules on Day 7). On Days 1-6, participants will take 1 folic acid capsule.

Participants in the placebo group will slowly increase the number of placebo capsules they take in the first month. In the first week, participants will take 1 placebo capsule on Day 7, in the second and third week they will take 2 placebo capsules on Day 7, and in the fourth week they will take 3 placebo capsules on Day 7. On Days 1-6, participants will take 1 folic acid capsule.

Store study medications at room temperature between 59° to 86°F (15° to 30°C) and keep them away from light.

Keep these and all medicines out of the reach of children.

You will be asked to take the study drugs for 6 months, and your participation in the study will last approximately 8 months. The investigators will ask you to attend 12 study visits at the research center located at the Institute on Aging - Clinical \& Translational Research Building (IOA - CTRB):

  1. Screening Visit
  2. Baseline Visit
  3. Baseline Functional Magnetic Imaging (fMRI) Visit
  4. 1-Month Visit
  5. 2-Month Visit
  6. 3-Month Visit
  7. 4-Month Visit
  8. 5-Month Visit
  9. 6-Month Visit
  10. 6-Month fMRI Visit
  11. Follow-Up Visit I
  12. Follow-Up Visit II

The investigators will also call you approximately 9 times during the study to ask you how you feel and to find out if you remembered to take all your study drugs.

Conditions
Inflammation, Aging
Being tested
Methotrexate + Folic Acid, Placebo + Folic Acid, Functional MRI Experimental Tasks, Muscle Biopsy
Keywords
Aging, Cognitive Function, Physical Function, Systematic Inflammation, Methotrexate, Pain Symptoms
Medical subject headings
Inflammation, Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Methotrexate + Folic AcidDrug

    Also called Trexall, Rheumatrex

    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.

  • Placebo + Folic AcidDrug

    Also called Microcrystalline Cellulose

    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

  • Functional MRI Experimental TasksProcedure or surgery

    Also called - MRI, -Magnetic Resonance (MR), -Nuclear Magnetic Resonance (NMR) Imaging

    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.

  • Muscle BiopsyProcedure or surgery

    Also called -Biopsy, -Muscle Tissue Sample

    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.

Study groups in NCT02079948
Study groupRoleWhat they receive
Methotrexate + Folic AcidActive comparatorParticipants 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.
Receives: Procedure: Functional MRI Experimental Tasks; Procedure: Muscle Biopsy
Placebo + Folic AcidPlacebo comparatorParticipants 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.
Receives: Procedure: Functional MRI Experimental Tasks; Procedure: Muscle Biopsy
Functional MRI Experimental TasksExperimental15 participants will be randomly assigned to complete the fMRI visits at the baseline and 6 month.
Receives: Drug: Methotrexate + Folic Acid; Drug: Placebo + Folic Acid
Muscle BiopsyExperimental10 participants will be randomly assigned to complete the skeletal muscle tissue sample at the baseline and 6 month visits.
Receives: Drug: Methotrexate + Folic Acid; Drug: Placebo + Folic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 6 Months

Secondary outcomes (3)

  1. Physical Function

    To examine the effects of methotrexate on changes in physical function (walking speed, muscle fatigue, and strength).

    Measured: 6 Months

  2. Cognitive Performance

    To examine the effects of methotrexate on cognitive performance (attention and memory).

    Measured: 6 Months

  3. Pain Symptoms

    To examine the effects of methotrexate on pain symptoms.

    Measured: 6 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completionSep 2014
  4. Study completionSep 2014

Why it stopped: Potential participants had concerns about taking the study drug (methotrexate).

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02079948
Sponsor's protocol ID
1182013
Other IDs
P30AG028740
Acronym
ICE
Status last verified
Jan 2022
First submitted
4 Mar 2014
Last updated
11 Jan 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Methotrexate + Folic Acid, Functional MRI Experimental Tasks and Muscle Biopsy in people with Inflammation and Aging, run by University of Florida.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Markers of Systemic Inflammation (time frame: 6 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02079948.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2022.

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