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Regulatory T cells (Tregs) are a small population of T cells compromising of 1% to 5% of the total T cells in the body but they are playing a fundamental role in the maintenance of the immune homeostasis. These cells modulate the immune system by suppressing the effector activity and thus preventing autoimmune diseases and chronic inflammatory processes. Treg cell numbers have shown to increase with physical activity, and this increment has been directly correlated with exercise intensity. These results suggest that the increased Treg frequency may contribute to the beneficial effects of exercise on disorders associated with autoimmune disease or chronic low-grade inflammation such as atherosclerosis, diabetes mellitus, chronic kidney disease or cancer.
The overall purpose of this study is to determine the influence High-intensity interval training (HIIT) on the frequency and quality of peripheral Treg cells.
Tregs have been studied in clinical practice for different therapeutic applications. In the past several years there has been a significant interest in the transplant community to develop tolerance in order to substantially decrease or even eliminate the need of immuno-suppressive regimens. A growing body of evidence recognizes the balance between graft-reactive effector cells and graft-protective suppressor Treg cells as the ultimate determinant of long-term allograft survival. As a result, there is a major interest in transplantation to enhance the suppressor immune response as an alternative or complementary approach to reach a clinical tolerogenic state and preserve graft function. Exercise improves baseline immune function and helps to maintain immune homeostasis. Treg cell numbers have shown to increase with physical activity, and this increment has been directly correlated with exercise intensity. These results suggest that the increased Treg frequency may contribute to the beneficial effects of exercise on disorders associated with autoimmune disease or chronic low-grade inflammation such as atherosclerosis, diabetes mellitus, chronic kidney disease or cancer.
Primary Objectives: The overall purpose of this study is to determine the influence High-intensity interval training (HIIT) on the frequency and quality of peripheral Treg cells.
Secondary Objectives: Effects of HIIT in other T cell populations. Effects of HIIT in plasma concentration of inflammatory and metabolic markers. Effects of HIIT in obese vs lean.
Design: This is a prospective, single center, single-arm "pre-test/post-test" study designed to evaluate the safety, feasibility and initial efficacy of a 12-week HIIT regimen to increase the frequency and quality of peripheral Treg cells. All participants will have a pre-test (baseline) evaluation followed by a treatment and then a post-test.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All subjects will be in one arm | Experimental | Both Lean and Obese, End-Stage Renal Disease (ESRD) patients and normal volunteers will be in one arm, that will receive the High Intensity Interval Training intervention. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High Intensity Interval Training | Other | After the acclimatization session and assessment of eligibility, a graded exercise test (GXT) will be given to the participant. After checking their vitals, the HIIT program will be performed on recumbent cycles. The first two weeks of training will consist of a gradual ramp where subjects will perform a moderate intensity cycling program consisting of a 5-minute warm up followed by progressively longer continuous cycling starting at 15 minutes and progressing up to 30 minutes prior to starting the HIIT training. For the HIIT training subjects will perform 5 minutes of low to moderate steady state cycling to warm up. Following the warm up, the subjects will complete the 4x4 HIIT program. This will consist of 4 minutes of cycling at 85% of the subject's maximum heart rate (HR) followed by 4 minutes of a low intensity cycling period for recovery. |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline concentration of circulating Regulatory T cells (Tregs) in blood at 12 weeks post HIIT intervention | Change from baseline concentration of circulating Regulatory T cells (Tregs) in blood | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum C-Reactive protein at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Adiponectin at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline expansion rates of TRegs (in vitro) at 12 weeks post HIIT intervention | Change from baseline expansion rates of TRegs | Baseline- and at 12 weeks post-HIIT intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline Serum Interleukin-6 (IL6) at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Tumor Necrosis Factor- Alpha (TNF-alpha) at 12 weeks post HIIT intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline Serum IL10 at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Interferon Gamma (IFNg) at 12 weeks post HIIT intervention |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Francesc Marti, PhD | University of Kentucky, College of Medicine / Transplant Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky Transplant Center | Lexington | Kentucky | 40536 | United States |
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| ID | Term |
|---|---|
| D007676 | Kidney Failure, Chronic |
| D009043 | Motor Activity |
| D009765 | Obesity |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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| ID | Term |
|---|---|
| D000072696 | High-Intensity Interval Training |
| ID | Term |
|---|---|
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
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Change from baseline concentration of serologic cytokines/growth factors/metabolites |
| Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Leptin at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Blood Glucose at 12 weeks post HIIT intervention | Concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Triglycerides at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Total Cholesterol at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Low Density Lipoprotein (LDL) at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline High Density Lipoprotein (HDL) at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Insulin at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular Helios at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CD36 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane GLUT1 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane Leptin-Receptor at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane TIGIT at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Suppressor Activity at 12 weeks post HIIT intervention | Change from baseline activty of the Functional activity of TRegs | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular FoxP3 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Membrane CD25 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Membrane CD127 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the Treg phenotype marker | Baseline- and at 12 weeks post-HIIT intervention |
Change from baseline concentration of serologic cytokines/growth factors/metabolites |
| Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Epinephrine at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum NorEpinephrine at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Serum Lactate at 12 weeks post HIIT intervention | Change from baseline concentration of serologic cytokines/growth factors/metabolites | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular Eomes at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular RORyt at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular Tbet at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane OX40 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane GITR at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker ofTreg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane DR3 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane 41BB at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CCR2 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CCR4 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CCR6 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CCR7 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CXCR3 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CD226 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular CTLA4 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane ICOS at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane PD1 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane PDL1 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CD39 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane CD49d at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Cell membrane LAP-T at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular Granzyme-Beta at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker ofTreg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular IL35 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular IL10 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of Treg cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline TSRD-Met at 12 weeks post HIIT intervention | Changes from baseline methylation status of tsrd promoter - Treg lineage commitment | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular Tbet at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of conventional-Effector TH1 T cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular IFNg at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of conventional-Effector TH1 T cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular GATA3 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of conventional-Effector TH2 T cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular IL5 at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of conventional-Effector TH2 T cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular RORgt at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of conventional-Effector TH17 T cells | Baseline- and at 12 weeks post-HIIT intervention |
| Change from baseline Intracellular IL17af at 12 weeks post HIIT intervention | Change from baseline percentage and intensity of the phenotype marker of conventional-Effector TH17 T cells | Baseline- and at 12 weeks post-HIIT intervention |
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001519 | Behavior |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D009142 |
| Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |