Trial Outcomes & Findings for Understanding the Exercise-Hypertension Paradox (NCT NCT02034422)

NCT ID: NCT02034422

Last Updated: 2024-04-12

Results Overview

Blood pressure with be assessed prior to the study intervention and during exercise (Aim #1). Additionally, blood pressure will be assessed following 8 weeks of exercise rehabilitation

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 75 participants
• Primary outcome timeframe: Immediate to 8 weeks
• Results posted on: 2024-04-12

Participant Flow

Participant milestones

Measure	Specific Aim #1 Specific Aim 1: Determine the consequences of oxidative stress on skeletal muscle afferent feedback and muscle blood flow during exercise in hypertension. Hypothesis: Afferent feedback sensitivity, determined by passive leg movement (isolation of mechanoreceptor sensitivity) and post exercise circulatory occlusion (isolation of metaboreceptor sensitivity) will be greater in hypertension leading to the exaggerated EPR. Muscle blood flow, assessed by Doppler ultrasound during multiple exercise intensities, will be impaired in hypertension leading to exercise intolerance. Reductions in oxidative stress, achieved by an oral antioxidant treatment (Vitamins C, E and alpha lipoic acid), will reduce afferent fiber sensitivity and improve muscle blood flow in hypertension. Additionally, venous endothelial cells will express elevated markers of oxidative stress providing novel evidence that the vascular endothelium contributes to the greater oxidative stress in hypertension. Oral Antioxidant: Consisting of vitamins C, E and alpha lipoic acid.	Specific Aim #2 Specific Aim 2: Determine the remediable effect of combined antioxidant treatment and exercise rehabilitation in the treatment of hypertension. Hypothesis: Acute antioxidant treatment administered prior to exercise in hypertensive patients will ameliorate the exaggerated EPR resulting in a normal and safe blood pressure response to exercise-based rehabilitation. This two-pronged approach (antioxidants and exercise training) will result in a safely achieved reduction in skeletal muscle afferent feedback facilitating improved exercise tolerance, improved muscle blood flow and ultimately reduced cardiovascular risk in this population. Oral Antioxidant: Consisting of vitamins C, E and alpha lipoic acid. Exercise rehabilitation: 8 weeks of exercise rehabilitation
Overall Study STARTED	49	26
Overall Study COMPLETED	49	26
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Understanding the Exercise-Hypertension Paradox

Baseline characteristics by cohort

Measure	Specific Aim #1 n=49 Participants Specific Aim 1: Determine the consequences of oxidative stress on skeletal muscle afferent feedback and muscle blood flow during exercise in hypertension. Hypothesis: Afferent feedback sensitivity, determined by passive leg movement (isolation of mechanoreceptor sensitivity) and post exercise circulatory occlusion (isolation of metaboreceptor sensitivity) will be greater in hypertension leading to the exaggerated EPR. Muscle blood flow, assessed by Doppler ultrasound during multiple exercise intensities, will be impaired in hypertension leading to exercise intolerance. Reductions in oxidative stress, achieved by an oral antioxidant treatment (Vitamins C, E and alpha lipoic acid), will reduce afferent fiber sensitivity and improve muscle blood flow in hypertension. Additionally, venous endothelial cells will express elevated markers of oxidative stress providing novel evidence that the vascular endothelium contributes to the greater oxidative stress in hypertension. Oral Antioxidant: Consisting of vitamins C, E and alpha lipoic acid.	Specific Aim #2 n=26 Participants Specific Aim 2: Determine the remediable effect of combined antioxidant treatment and exercise rehabilitation in the treatment of hypertension. Hypothesis: Acute antioxidant treatment administered prior to exercise in hypertensive patients will ameliorate the exaggerated EPR resulting in a normal and safe blood pressure response to exercise-based rehabilitation. This two-pronged approach (antioxidants and exercise training) will result in a safely achieved reduction in skeletal muscle afferent feedback facilitating improved exercise tolerance, improved muscle blood flow and ultimately reduced cardiovascular risk in this population. Oral Antioxidant: Consisting of vitamins C, E and alpha lipoic acid. Exercise rehabilitation: 8 weeks of exercise rehabilitation	Total n=75 Participants Total of all reporting groups
Age, Continuous	51 years STANDARD_DEVIATION 12 • n=5 Participants	53 years STANDARD_DEVIATION 10 • n=7 Participants	52 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	20 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	22 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Blood Pressure	103 mmHg STANDARD_DEVIATION 9 • n=5 Participants	106 mmHg STANDARD_DEVIATION 13 • n=7 Participants	104 mmHg STANDARD_DEVIATION 11 • n=5 Participants

PRIMARY outcome

Timeframe: Immediate to 8 weeks

Blood pressure with be assessed prior to the study intervention and during exercise (Aim #1). Additionally, blood pressure will be assessed following 8 weeks of exercise rehabilitation

Outcome measures

Measure	Specific Aim #1 n=49 Participants Specific Aim 1: Determine the consequences of oxidative stress on skeletal muscle afferent feedback and muscle blood flow during exercise in hypertension. Hypothesis: Afferent feedback sensitivity, determined by passive leg movement (isolation of mechanoreceptor sensitivity) and post exercise circulatory occlusion (isolation of metaboreceptor sensitivity) will be greater in hypertension leading to the exaggerated EPR. Muscle blood flow, assessed by Doppler ultrasound during multiple exercise intensities, will be impaired in hypertension leading to exercise intolerance. Reductions in oxidative stress, achieved by an oral antioxidant treatment (Vitamins C, E and alpha lipoic acid), will reduce afferent fiber sensitivity and improve muscle blood flow in hypertension. Additionally, venous endothelial cells will express elevated markers of oxidative stress providing novel evidence that the vascular endothelium contributes to the greater oxidative stress in hypertension. Oral Antioxidant: Consisting of vitamins C, E and alpha lipoic acid.	Specific Aim #2 n=26 Participants Specific Aim 2: Determine the remediable effect of combined antioxidant treatment and exercise rehabilitation in the treatment of hypertension. Hypothesis: Acute antioxidant treatment administered prior to exercise in hypertensive patients will ameliorate the exaggerated EPR resulting in a normal and safe blood pressure response to exercise-based rehabilitation. This two-pronged approach (antioxidants and exercise training) will result in a safely achieved reduction in skeletal muscle afferent feedback facilitating improved exercise tolerance, improved muscle blood flow and ultimately reduced cardiovascular risk in this population. Oral Antioxidant: Consisting of vitamins C, E and alpha lipoic acid. Exercise rehabilitation: 8 weeks of exercise rehabilitation
Blood Pressure Baseline blood Pressure	103 mmHg Standard Deviation 9	106 mmHg Standard Deviation 13
Blood Pressure Post treatment blood pressure	94 mmHg Standard Deviation 9	101 mmHg Standard Deviation 12

Adverse Events

Specific Aim #1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Specific Aim #2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Joel Trinity, PhD

Salt Lake City VAMC

Phone: 801-582-1565

Email: joel.trinity@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place