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WithdrawnNCT04774484Updated Feb 14, 2023

High-Intensity Interval Training and Regulatory T Cells

An interventional study of High Intensity Interval Training in End Stage Renal Disease, sponsored by Francesc Marti. Withdrawn at 1 site in United States. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-02-14.

Sponsored by Francesc Marti · Not applicable, Interventional, and Treatment

Why this study was withdrawn
Funding was not available.
Phase
Not applicable
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • End Stage Renal Disease

Keywords

  • high intensity
  • interval training
  • exercise
  • obesity
  • inflammation
  • Treg
03

In context

Kidney Failure, Chronic

2,085 studies on the registry are indexed under Kidney Failure, Chronic; 261 are open to participants now.

Browse Kidney Failure, Chronic studies →

Lead sponsor

This is the only study on the registry with Francesc Marti as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Age between 18 and 65 years old.
  • BMI between 18.5 and 25 or above 30. Rationale: we want to include "obesity" as categorical covariate in the influence of HIIT and discriminate the participants between "lean" (BMI range 18.5-25) and "obese" (BMI > 30)
  • Sedentary lifestyle (fewer than 5,000 steps per day)
  • Fluent in English, able to understand and provide informed consent.
  • Subjects willing to participate in the study and comply with study requirements as evidenced by signed Institutional Review Board (IRB)-approved informed consent.

Exclusion criteria

Exclusion Criteria:

  • Age under 18 or over 65
  • BMI under 18.5 or between 25 and 30.
  • Active lifestyle (more than 5,000 steps per day).
  • Previous chronic use of systemic glucocorticoids, immune-suppressors or immuno-modulators in the preceding 3 months.
  • Patients with significant or active infection: HIV negative by ELISA or reverse transcription polymerase chain reaction (RT-PCR) [if ELISA is positive and RT-PCR is negative, the ELISA is considered false positive]; negative serology for Hepatitis B and C.
  • Active malignancy or history of malignancy within 1 year.
  • Be pregnant or breastfeeding.
  • Hemoglobin less than 9.0 g/dl at the time of blood drawing.
  • Platelet count less than 100,000/* at the time of blood drawing.
  • White blood count less than 4 and/or Absolute Neutrophil Count less than 1500/* at the time of blood drawing.
  • Participation in any other study that involved investigational drug or regimens in the preceding 12 months.
  • History of delayed or abnormal wound healing.
  • Any immuno-related condition, chronic illness or prior treatment which, in the opinion of the investigator, precludes study participation.
  • Inability or unwillingness of participant to comply with study protocol or procedures.
  • Impaired consent capacity.
  • Any chronic use of anticoagulation.
  • Recipient of blood transfusion in 3 months prior to blood drawing.
  • Any orthopedic condition or chronic pain that prevents them from cycling.
  • Any symptomatic coronary artery disease prior enrollment within 3 months or any intervention for it in the past 6 months.
  • Any symptomatic current heart failure (New York Heart Association class III and IV), significant valvar heart disease.
  • History of non-compliance.
  • The study will not include any vulnerable population such as fetuses, pregnant women, children, or prisoners.
05

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    All subjects will be in one arm

    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.

    Other: High Intensity Interval Training

Interventions

  • OtherHigh Intensity Interval Training

    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.

06

What researchers measure

Primary outcomes

  1. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  2. Change from baseline Serum C-Reactive protein at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  3. Change from baseline Serum Adiponectin at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  4. Change from baseline expansion rates of TRegs (in vitro) at 12 weeks post HIIT intervention

    Change from baseline expansion rates of TRegs

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

Secondary outcomes

  1. Change from baseline Serum Interleukin-6 (IL6) at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  2. Change from baseline Serum Tumor Necrosis Factor- Alpha (TNF-alpha) at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  3. Change from baseline Serum Leptin at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  4. Change from baseline Blood Glucose at 12 weeks post HIIT intervention

    Concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  5. Change from baseline Serum Triglycerides at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  6. Change from baseline Total Cholesterol at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  7. Change from baseline Low Density Lipoprotein (LDL) at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  8. Change from baseline High Density Lipoprotein (HDL) at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  9. Change from baseline Serum Insulin at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  10. Change from baseline Intracellular Helios at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  11. Change from baseline Cell membrane CD36 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  12. Change from baseline Cell membrane GLUT1 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  13. Change from baseline Cell membrane Leptin-Receptor at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  14. Change from baseline Cell membrane TIGIT at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  15. Change from baseline Suppressor Activity at 12 weeks post HIIT intervention

    Change from baseline activty of the Functional activity of TRegs

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  16. Change from baseline Intracellular FoxP3 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  17. Change from baseline Membrane CD25 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  18. Change from baseline Membrane CD127 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the Treg phenotype marker

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

Other outcomes

  1. Change from baseline Serum IL10 at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  2. Change from baseline Serum Interferon Gamma (IFNg) at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  3. Change from baseline Serum Epinephrine at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  4. Change from baseline Serum NorEpinephrine at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  5. Change from baseline Serum Lactate at 12 weeks post HIIT intervention

    Change from baseline concentration of serologic cytokines/growth factors/metabolites

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  6. Change from baseline Intracellular Eomes at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker of Treg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  7. Change from baseline Intracellular RORyt at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker of Treg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  8. Change from baseline Intracellular Tbet at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker of Treg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  9. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  10. Change from baseline Cell membrane GITR at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker ofTreg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  11. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  12. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  13. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  14. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  15. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  16. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  17. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  18. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  19. Change from baseline Intracellular CTLA4 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker of Treg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  20. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  21. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  22. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  23. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  24. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  25. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  26. Change from baseline Intracellular Granzyme-Beta at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker ofTreg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  27. Change from baseline Intracellular IL35 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker of Treg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  28. Change from baseline Intracellular IL10 at 12 weeks post HIIT intervention

    Change from baseline percentage and intensity of the phenotype marker of Treg cells

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  29. Change from baseline TSRD-Met at 12 weeks post HIIT intervention

    Changes from baseline methylation status of tsrd promoter - Treg lineage commitment

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  30. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  31. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  32. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  33. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  34. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

  35. 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

    Time frame: Baseline- and at 12 weeks post-HIIT intervention

07

Study locations

1 site
  • University of Kentucky Transplant Center
    Lexington, Kentucky 40536, United States
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 14, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT04774484
Lead sponsor
Francesc Marti
Responsible party
Francesc Marti (Associate Professor, University of Kentucky) — Sponsor-investigator
First posted
Mar 1, 2021
Start date
Jan 2023 (estimated)
Primary completion
Jun 30, 2026 (estimated)
Completion
Jun 30, 2026 (estimated)
Last update
Feb 14, 2023

Study contacts

Francesc Marti, PhD
principal investigator · University of Kentucky, College of Medicine / Transplant Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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