Physical Activity in Renal Disease (PAIRED): The Effect on Hypertension

NCT03551119 | Terminated Phase 3 DMC

• 1 other identifier: Pro00078564
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 3

Brief Summary

Background and importance: Hypertension is highly prevalent among Canadians with non-dialysis dependent chronic kidney disease (CKD). It is a modifiable risk factor for both cardiovascular (CV) events and CKD progression. Exercise is an effective strategy for blood pressure (BP) reduction in the general population but in people with CKD, hypertension is mediated by different causes (i.e. vascular stiffness, volume expansion) and it is unclear whether exercise will reduce BP in this population. Consequently, exercise resources are not offered in the routine multidisciplinary care of people with CKD and the prevalence of sedentary behaviour remains double that of the general population. The role of exercise in CKD management is also an important question for patients. From CIHR-supported workshops with patients, the role of lifestyle, such as exercise in CKD was a top research priority. Research aims: i.To determine the effect of exercise on mean ambulatory systolic blood pressure (SBP) in people with CKD compared to usual care. The investigators hypothesize that exercise training will significantly reduce BP compared to control. ii.To inform the design of a larger, multi-center trial evaluating the effect of exercise on the risk of CKD progression. Methods: A 160 participant, single center randomized trial of adults from Alberta Kidney Care North CKD clinics, Edmonton, Albert, Canada. Participants with an estimated glomerular filtration rate (eGFR) of 15-44 ml/min per 1.73m2 and SBP \>130 mmHg will be randomized, stratified by eGFR (\<30 versus ≥ 30) to an exercise intervention or usual care. The main outcome is the difference in 24-hour ambulatory SBP after eight weeks of exercise training between groups. Secondary outcomes include: BPs at eight and 24 weeks, dose of anti-hypertensives, aortic stiffness, CV-risk markers, CV fitness, 7-day accelerometry, quality of life, safety, and in an exploratory analysis, eGFR and proteinuria. The intervention is thrice weekly moderate intensity aerobic exercise supplemented with isometric resistance exercise, targeting 150 minutes per week and delivered over 24-weeks. Phase 1: one supervised weekly sessions and home-based sessions (eight weeks). Phase 2: home-based sessions (16 weeks). To detect a clinically important BP reduction of 5 mmHg between groups requires 128 patients (two sample t-test, alpha 0.05, beta 0.2, common standard deviation of 10 mmHg). Assuming 20% dropout requires 160 patients. For the primary outcome, the investigators will use a mixed linear regression model in which BP is regressed on group, baseline SBP and eGFR, and time point. Expected outcomes: The findings from this study will address a significant knowledge gap in hypertension management in CKD, inform care-delivery and the design of a larger study on CKD progression. This proposal aligns with priorities for both patients and decision makers: to identify the role of exercise in CKD management and to reshape the delivery of renal care so that it is more consistent with patient values and preferences.

Conditions

Chronic Kidney Diseases

Outcome Measures

Primary Outcomes (1)

• 24-hour ambulatory SBP

  mean 24-hour ambulatory systolic blood pressure

  8 weeks

Secondary Outcomes (30)

• antihypertensive use

  8 and 24 weeks

• KDQOL-36

  8 and 24 weeks

• IPAQ-SF

  8 and 24 weeks

• SEE scale

  8 and 24 weeks

• EQ-5D

  8 and 24 weeks

Study Arms (2)

Exercise

EXPERIMENTAL

Personnel experienced in training people with chronic conditions (exercise specialist) will supervise the exercise training. At each in-center session in phase 1, the patient's exercise will be monitored to assess whether they are achieving target levels. Training intensities will be prescribed based on the most recent exercise test. Phase 1: an eight-week program of once weekly-supervised facility-based exercise sessions and twice weekly home-based sessions. Phase 2: a 16-week home-based exercise program overseen by an exercise specialist. During this phase, participants will be progressed through their home-based exercise program from Phase 1 on an individual basis. i. Frequency. A minimum of three exercise sessions per week. ii. Intensity. A moderate intensity (40-60% heart rate reserve) based on exercise testing. iii. Time. 150 minutes of exercise per week. iv. Type. We will prescribe aerobic exercise supplemented with isometric resistance exercises.

Behavioral: Exercise

Enhanced usual care

OTHER

Participants in the control group will perform accelerometry. This is enhanced usual care because physical activity measurement is not routinely performed in CKD clinics. Control arm participants will only receive their accelerometry data after they have completed the study.

Other: Enhanced usual care

Interventions

Exercise BEHAVIORAL

See previous description

Exercise

Enhanced usual care OTHER

See previous description

Enhanced usual care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Resting SBP \>120 mmHg systolic on screening BP clinic measurements (with an electronic sphygmomanometer, mean of three readings after first reading is discarded) and at least one previous SBP measurement above 120 mmHg on a separate occasion within the past six months (home or clinic measurement).
• Stable on blood pressure medications for the past eight weeks
• eGFR 15-44 ml/min per 1.73m2 eGFR between 15-44 ml/min per 1.73m2 within the last three months and one additional value in this rage in the last 12 months.
• Independent ambulation with or without an assistive device for at least three consecutive minutes
• Cognition and English language sufficient enough to understand written information, provide consent, and comply with the testing and interventions
• Approval of the attending nephrologist
• No significant exercise-induced arrhythmia or new ischemia on submaximal incremental exercise testing (final screening step)

You may not qualify if:

• Resting SBP \>160 mmHg or DBP \> 110 mmHg on screening BP clinic measurement (Note: the individual may be re-screened 8 weeks after medication adjustment)
• Arm circumference greater than 54 centimeters (size limit of large ABPM cuff)
• Recent (\<6 weeks) or planned (\<6 months) major cardiovascular events or procedures
• Any known contraindication to exercise (American College of Sports Medicine Guidelines)
• Acute myocardial infarction (3-5 days) or unstable angina; Uncontrolled symptomatic arrhythmias; Active endocarditis; Acute myocarditis or pericarditis; Symptomatic severe aortic stenosis; Acute pulmonary embolism or deep vein thrombosis; Suspected dissecting aneurysm; Uncontrolled asthma; Uncontrolled pulmonary edema; Room air desaturation to \<85%; Acute non-cardiopulmonary disorder that may affect exercise performance (infection, orthopedic problem); Mental impairment leading to inability to cooperate; Uncontrolled hypertension (as above)
• Pregnant or planning to become pregnant
• Transplant
• Life expectancy or predicted time to renal replacement therapy \<9 months (attending physician judgment)
• Planned move or hospital admission within the next 9 months
• Currently enrolled in an interventional clinical trial; currently enrolled in a structured exercise program or performing regular exercise training \> 2 day/week in the last 3 months
• Taking other medications known to affect blood pressure (prednisone cyclosporine) and expected adjustment in the next 9 months
• Significant barrier to participation in a home exercise program or an insurmountable barrier to attend in-center training sessions.

Sponsors & Collaborators

• University of Alberta: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (3)

Royal Alexandra Hospital

Edmonton, Alberta, T5H 3V9, Canada

Location

University of Alberta Hospital, outpatient dialysis unit

Edmonton, Alberta, T6G 2P4, Canada

Location

Grey Nuns Hospital

Edmonton, Alberta, T6L5X8, Canada

Location

Related Publications (1)

• Thompson S, Wiebe N, Gyenes G, Davies R, Radhakrishnan J, Graham M. Physical Activity In Renal Disease (PAIRED) and the effect on hypertension: study protocol for a randomized controlled trial. Trials. 2019 Feb 8;20(1):109. doi: 10.1186/s13063-019-3235-5.

  PMID: 30736832 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Exercise

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Stephanie Thompson, MD PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the intervention, participants cannot be blinded to group assignment; however, the primary outcome is objectively measured (24-hour ambulatory blood pressure measurement). For main trial secondary outcomes, assessors will be blinded to allocation status.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: In this parallel arm control trial, participants recruited from outpatient CKD clinics in Alberta Kidney Care North, Edmonton, Alberta, Canada will be randomized (1:1) to enhanced usual care (measurement of physical activity levels) or an exercise intervention.

Study Record Dates

• First Submitted: May 12, 2018
• First Posted: June 11, 2018
• Study Start: November 21, 2018
• Primary Completion: August 13, 2020
• Study Completion: August 20, 2020
• Last Updated: April 30, 2021

Record last verified: 2021-04

Locations

CA (3)