RecruitingEarly Phase 1NCT06643221

Exercise as an Immune Adjuvant for Allogeneic Cell Therapies

Exercise-induced Adrenergic Receptor Signaling as an Immune Adjuvant for Allogeneic Cell Therapies


Sponsor

University of Arizona

Enrollment

100 participants

Start Date

Jan 24, 2018

Study Type

INTERVENTIONAL

Conditions

Summary

This study aims to improve the treatment of blood cancer by using exercise to collect healthier immune cells from donors. Allogeneic adoptive cell therapy is a treatment where immune cells from a healthy donor are given to a cancer patient, usually to help prevent or treat cancer relapse after a stem cell transplant. These donor cells can either be directly infused into the patient or grown in a lab to create more specialized immune cells that target and kill cancer. While this therapy has been helpful for many patients, there is a need to make it more effective for a larger group and reduce side effects like graft-versus-host disease (GvHD), where the donor's immune cells attack the patient's healthy tissue. This Early Phase 1 trial will test whether exercise can help produce better immune cells from donors. The investigators will recruit healthy participants for three study groups: 1. Exercise Group: Participants will complete a 20-minute cycling exercise session. The investigators will collect blood samples before, during, and after exercise to study the number and quality of immune cells. The investigators will also use the collected cells to create immune therapies and test their ability to kill cancer cells in the lab and control cancer growth in mice. 2. Exercise and Beta Blocker Group: In this group, participants will complete up to five cycling sessions, with at least a week between each session. Before each session, participants will take either a placebo or a drug (beta blocker) that blocks stress hormones like adrenaline. The investigators will collect blood samples before and during exercise to see how blocking these hormones changes the effect of exercise on immune cells. 3. Isoproterenol Group: Participants in this group will receive a 20-minute infusion of isoproterenol, a drug that mimics the effects of adrenaline. The investigators will collect blood samples before, during, and after the infusion to see if the drug causes similar immune changes to those caused by exercise. Participants can join one, two, or all three groups. This research will help understand whether exercise can improve immune cell therapies for treating blood cancer and reduce the risk of GvHD, making these treatments safer and more effective.


Eligibility

Min Age: 21 YearsMax Age: 55 Years

Plain Language Summary

Simplified for easier understanding

This study is investigating whether exercise causes the body to release immune cells that could enhance the effectiveness of allogeneic cell therapies (treatments using donor cells). Researchers are also testing how a medication that mimics the effect of exercise on the heart (isoproterenol) compares to actual exercise in releasing these immune cells. **You may be eligible if...** - You are between 21 and 55 years old - You are considered "low risk" for a graded exercise or stress test (generally healthy with no more than one heart disease risk factor) - You have no contraindications to several specific medications used in the study **You may NOT be eligible if...** - You currently smoke or have quit within the last 6 months - Your BMI is over 34 or your waist size exceeds certain measurements - You take medications that affect the immune system or blood pressure - You are pregnant or breastfeeding - You have chronic arthritis, have been bedridden recently, or had a recent illness - You have cardiovascular disease, HIV, hepatitis, or an autoimmune disease - You have asthma, kidney disease, diabetes, or a history of severe allergic reactions Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BEHAVIORALExercise

After an initial maximal graded exercise test to determine maximal oxygen uptake and peak cycling power, healthy participants will undergo a 20-minute graded exercise test at intensities corresponding to 50, 60, 70 and 80% VO2max (5-minutes per stage)

DRUGIsoproterenol

To determine if pharmacological activation of beta-adrenergic receptors evokes an immune respponse akin to exercise, healthy participants will receive an intravenous infusion of isoproterenol (50ng/kg/min)

DRUGPlacebo

Healthy participants will consume the placebo 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake

DRUGBisoprolol Fumarate Tablet 10 mg

Healthy participants will consume a 10mg Bisoprolol Fumerate tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake

DRUGNadolol (1 x 80 mg) Tablets (Invamed, Inc)

Healthy participants will consume a 80mg Nadolol tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake

DRUGCarvedilol 50 mg

Healthy participants will consume a 50mg Carvedilol tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake

DRUGRoflumilast 500 Mcg Oral Tablet

Healthy participants will consume a 500mcg Roflumilast tablet and a 10mg Bisoprolol tablet 2-3h prior to completing a 20-minute graded exercise test at intensities ranging from 50-80-% of the maximal oxygen uptake


Locations(1)

The University of Arizona

Tucson, Arizona, United States

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NCT06643221


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