Orthostatic Intolerance After Bariatric Surgery (RYGB)

June 10, 2024 updated by: Cyndya Shibao, MD, Vanderbilt University Medical Center
More than 78 million adults in the U.S. are obese. Bariatric surgery is the only modality that results in sustained weight loss along with reversal of diabetes mellitus, and a decrease in cardiovascular events. Obesity is associated with increased sympathetic nervous system (SNS) activity that contributes to blood pressure regulation; sympathetic vasoconstrictor activity is maximally activated upon standing and is fundamental for the maintenance of orthostatic tolerance. After bariatric surgery, there is a significant and sustained reduction in SNS activity at three and six months after the procedure, which is related to weight loss. Recently, multiple retrospective studies have reported an orthostatic intolerance (OI) syndrome after bariatric surgery characterized by chronic pre-syncopal symptoms, syncope and orthostatic hypotension. In the Vanderbilt University Medical Center bariatric surgical center, 741 post-bariatric surgery patients reported OI symptoms, 98 (13.2%) of these patients, progressed to chronic OI and in17 cases, the OI was so disabling that patients initiated treatment with pressor agents. More than 50% of OI cases in the cohort developed the condition during a weight-stable period. Hence, investigators propose the novel hypothesis that after bariatric surgery, the persistent reduction in SNS activity contributes to impaired orthostatic tolerance, which is independent of weight loss.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Considering that SNS vasoconstrictor activity depends on synaptic norepinephrine concentrations, investigators propose a proof-of-concept study to test the hypothesis that the norepinephrine transporter (NET) inhibitor, atomoxetine, which increases synaptic norepinephrine concentrations, will improve post-bariatric OI. Understanding the changes in SNS activity and its contribution to orthostatic tolerance after bariatric surgery is of utmost importance to unravel the mechanisms of a novel and unrecognized syndrome, post-bariatric OI. In 2014, nearly 200,000 individuals in the US underwent bariatric surgery, and the number of bariatric surgery procedures is expected to increase by 22% each year. It is projected, therefore, an increase in the incidence of post-bariatric OI.

Participants with Roux-en-Y gastric bypass (RYGB) and Vertical sleeve gastrectomy (VSG) will be studied.

OI is a chronic and disabling condition; treatment is challenging because current therapies have debatable efficacy.

The proposed application will not only provide central knowledge on the pathophysiology of this new syndrome but also will fill an unmet therapeutic need by repurposing NET inhibitors for the treatment of OI.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37027
        • Cyndya Shibao

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Obese subjects that will undergo bariatric surgery or medical weight loss.
  • Age 18-60 years
  • BMI >35 kg/m2
  • Weight < 400 lbs

Exclusion Criteria:

  • Diabetes type 1
  • Use of an alpha blockers, clonidine, beta-blockers.
  • Pregnancy or breast-feeding. Women of childbearing potential will be required to have undergone tubal ligation or to be using an oral contraceptive or barrier methods of birth control.
  • The use of any strong CYP2D6 inhibitor (e.g., fluoxetine, paroxetine, quinidine, tipranavir).
  • Use of selective NET inhibitors.
  • Use of monoamine oxidase inhibitors.
  • Cardiovascular disease such as myocardial infarction within six months prior to the study, presence of angina pectoris, significant arrhythmia, congestive heart failure (left ventricular hypertrophy acceptable), deep vein thrombosis, pulmonary embolism, second or third degree heart block, mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy
  • History of serious neurologic disease such as cerebral hemorrhage, stroke, or transient ischemic attack
  • Hematocrit < 34%
  • Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
  • Mental conditions rendering a subject unable to understand the nature, scope and possible consequences of the study
  • Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, unlikelihood of completing the study, and investigator discretion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Roux-en-Y gastric bypass (RYGB)/Atomoxetine
Participants with standard of care RYGB will receive atomoxetine, 0.5 mg/kg/day for 3 days
Drug: Atomoxetine
atomoxetine 0.5 mg/kg/day.
Other Names:
  • strattera
Experimental: Vertical sleeve gastrectomy (VSG) /Atomoxetine
Participants with standard of care VSG will receive atomoxetine 0.5 mg/kg/day for 3 days
Drug: Atomoxetine
atomoxetine 0.5 mg/kg/day.
Other Names:
  • strattera
Placebo Comparator: Roux-en-Y gastric bypass (RYGB)/Placebo
Participants with standard of care RYGB will receive placebo 0.5 mg/kg/day for 3 days
Drug: Placebo
sugar pill
Other Names:
  • sugar pill
Placebo Comparator: Vertical sleeve gastrectomy (VSG)/ Placebo
Participants with standard of care VSG will receive placebo 0.5 mg/kg/day for 3 days
Drug: Placebo
sugar pill
Other Names:
  • sugar pill

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Blood Pressure Measurements During Orthostatic Challenge With a Head up Tilt (HUT at 60 Degrees) Before and After Bariatric Surgery: at 2 Timepoints: After 10% Weight Loss and After 3 Months
Time Frame: 0- 3 months

To assess the hemodynamic (Blood Pressure) changes during an orthostatic challenge with a head up tilt (HUT at 60 degrees) before and after bariatric surgery, at two time-points: after 10% weight loss (10% WL) and after 3 months, in morbidly obese patients.

Our primary endpoint (orthostatic tolerance, OT) is defined as the time between the start of the 60 degree HUT until pre-syncope Orthostatic hemodynamics were analyzed as the area under the curve (AUC) after baseline-correction during HUT.
0- 3 months
Cardiac Output During Orthostatic Challenge With a Head up Tilt (HUT at 60 Degrees) Before and After Bariatric Surgery: at 2 Timepoints: After 10% Weight Loss and After 3 Months
Time Frame: 0- 3 months

To assess the hemodynamic (cardiac output [CO]) and cardiovascular autonomic changes during an orthostatic challenge with a head up tilt (HUT at 60 degrees) before and after bariatric surgery, at two time-points: after 10% weight loss (10% WL) and after 3 months, in morbidly obese patients.

Our primary endpoint (orthostatic tolerance, OT) is defined as the time between the start of the 60 degree HUT until pre-syncope Orthostatic hemodynamics were analyzed as the area under the curve (AUC) after baseline-correction during HUT.
0- 3 months
Stroke Volume Measurements During Orthostatic Challenge With a Head up Tilt (HUT at 60 Degrees) Before and After Bariatric Surgery: at 2 Timepoints: After 10% Weight Loss and After 3 Months
Time Frame: 0- 3 months

To assess the hemodynamic (stroke volume [SV]) and cardiovascular autonomic changes during an orthostatic challenge with a head up tilt (HUT at 60 degrees) before and after bariatric surgery, at two time-points: after 10% weight loss (10% WL) and after 3 months, in morbidly obese patients.

Our primary endpoint (orthostatic tolerance, OT) is defined as the time between the start of the 60 degree HUT until pre-syncope Orthostatic hemodynamics were analyzed as the area under the curve (AUC) after baseline-correction during HUT.
0- 3 months
Calculated Total Peripheral Resistance During Orthostatic Challenge With a Head up Tilt (HUT at 60 Degrees) Before and After Bariatric Surgery: at 2 Timepoints: After 10% Weight Loss and After 3 Months
Time Frame: 0- 3 months

To assess the hemodynamic ( total peripheral resistance [TPR]) and cardiovascular autonomic changes during an orthostatic challenge with a head up tilt (HUT at 60 degrees) before and after bariatric surgery, at two time-points: after 10% weight loss (10% WL) and after 3 months, in morbidly obese patients.

Our primary endpoint (orthostatic tolerance, OT) is defined as the time between the start of the 60 degree HUT until pre-syncope
0- 3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Norepinephrine transporter Inhibition
Time Frame: baseline and 30 minutes
the ratio of dihydroxyphenylglycol (DHPG) to Norepinephrine is used as the biomarker for NET inhibition
baseline and 30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vanderbilt University Medical Center

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cyndya Shiabao, M.D., Vanderbilt University Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 31, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 16, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 18, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 27, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 10, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 180499

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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