Effect of Exercise in OI

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00770484
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Duration (Months): 77.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main limitation patients with orthostatic intolerance (OI, or postural tachycardia syndrome, POTS) have to exercise is related to their increase in heart rate when standing. Main pharmacological treatment today is aimed at reducing heart rate with the use of betablockers (propanolol), this theoretically could also improve their exercise capacity; if their heart rate do not increase as much with the medication, they could exercise more. In addition, it has been suggested that in healthy volunteers subjected to head down tilt for 2 weeks (situation that produces a "simulated" transient POTS-like state) a single bout of intense exercise can improve orthostatic tolerance the day after exercising. The mechanisms involved in such response are not that clear but could be an increase in plasma volume already diminished in POTS patients. It seems likely that the same could be true for POTS patients.

The purpose of the present study are to pharmacologically improve the amount of exercise POTS patients can perform by reducing their baseline heart rate (specific aim 1) and to evaluate next day heart responses to an acute bout of intense exercise.

Therefore, the specific aims of this study are:

1. To test the hypothesis that lowering heart rate response with propanolol will result in an increase in exercise capacity.

2. To test the hypothesis that a single bout of exercise will result in an improvement in orthostatic tolerance the day after exercising.

Condition or Disease	Intervention/Treatment	Phase
Orthostatic Intolerance; Postural Tachycardia Syndrome	Drug: Propranolol then Placebo; Drug: Placebo then Propranolol	N/A

Detailed Description

• Subjects will be studied twice, once after receiving placebo and in a second occasion after receiving propanolol.

• An exercise capacity test with estimation of maximal oxygen consumption (VO2 max) will be done within 1 hour of receiving a pill containing placebo and that will be in appearance identical to the one for propanolol. This test will be conducted on a stationary bicycle and the effort will be gradually increased while expired air is measured during exhaustive physical work. The test will last approximately 30 minutes and be conducted in Vanderbilt's Clinical Trial Center.

• The day before and the day after the exercise test subjects will be asked to collect urine for 12 hours each time and to keep a record of how much liquid they ingest.

• Posture study tests (measurements of heart rate and blood pressure taken while lying down and at intervals for up to 30 minutes while standing) will be done the day before and the day after the exercise test.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Exercise in Orthostatic Intolerance
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Propranolol then placebo Active treatment	Drug: Propranolol then Placebo; Propanolol 20 mg, given orally within 1 hour prior to exercising; Other Names: Active
Placebo Comparator: Placebo then propranolol Placebo Treatment	Drug: Placebo then Propranolol; Placebo, matching pill given orally within 1 hour prior to exercising; Other Names: Inactive

Outcome Measures

Primary Outcome Measures

1. Maximal Oxygen Consumption Capacity (VO2 Max) [Over approximately 30 minutes, within 2 hours of receiving each intervention.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meet diagnostic criteria of POTS (Raj, et al., 2005)

• Age between 18-65 years

• Male and female are eligible (although the majority of patients POTS are female).

• Able and willing to provide informed consent

Exclusion Criteria:

• Presence of medical conditions that can explain postural tachycardia (e.g., dehydration, medications)

• Pregnancy

• Other factors which in the investigator's opinion would prevent the subject from completing the protocol.

• Patients who are bedridden or chair-ridden.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University

Investigators

• Principal Investigator: Italo Biaggioni, MD, Vanderbilt University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00770484
• Other Study ID Numbers: 080722
• First Posted: Oct 10, 2008
• Last Update Posted: Aug 5, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Italo Biaggioni, Professor of Medicine and Pharmacology, Vanderbilt University: Exercise; Propanolol; Beta blockers
• Additional relevant MeSH terms: Postural Orthostatic Tachycardia Syndrome; Orthostatic Intolerance; Tachycardia; Propranolol

Study Results

Participant Flow

Arm/Group Title	Propranolol Then Placebo	Placebo Then Propranolol
Arm/Group Description	Active treatment Propranolol then Placebo: Propanolol 20 mg, given orally within 1 hour prior to exercising	Placebo Treatment Placebo then Propranolol: Placebo, matching pill given orally within 1 hour prior to exercising
Period Title: Overall Study
STARTED	8	4
COMPLETED	7	4
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Propranolol Then Placebo	Placebo Then Propranolol	Total
Arm/Group Description	Active treatment Propranolol then Placebo: Propanolol 20 mg, given orally within 1 hour prior to exercising	Placebo Treatment Placebo then Propranolol: Placebo, matching pill given orally within 1 hour prior to exercising	Total of all reporting groups
Overall Participants	8	4	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	4 100%	12 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31 (3)	32 (2)	32 (3)
Sex: Female, Male (Count of Participants)
Female	8 100%	4 100%	12 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	8 100%	4 100%	12 100%

Outcome Measures

1. Primary Outcome

Title	Maximal Oxygen Consumption Capacity (VO2 Max)
Time Frame	Over approximately 30 minutes, within 2 hours of receiving each intervention.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Propranolol	Placebo
Arm/Group Description	Active treatment Propranolol then Placebo: Propanolol 20 mg, given orally within 1 hour prior to exercising	Placebo Treatment Placebo then Propranolol: Placebo, matching pill given orally within 1 hour prior to exercising
Measure Participants	11	11
Mean (Standard Error) [mL/kg/min]	27.6 (1)	24.5 (0.7)

Adverse Events

Arm/Group Title	Propranolol Then Placebo		Placebo Then Propranolol
Arm/Group Description	Active treatment Propranolol then Placebo: Propanolol 20 mg, given orally within 1 hour prior to exercising		Placebo Treatment Placebo then Propranolol: Placebo, matching pill given orally within 1 hour prior to exercising
All Cause Mortality
	Propranolol Then Placebo		Placebo Then Propranolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Propranolol Then Placebo		Placebo Then Propranolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Propranolol Then Placebo		Placebo Then Propranolol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.