Back to results

Orthostatic Intolerance After Bariatric Surgery (RYGB)

Primary Purpose

Orthostatic Intolerance

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Atomoxetine

Placebo

About this trial

This is an interventional treatment trial for Orthostatic Intolerance

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Cyndya Shibao

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Roux-en-Y gastric bypass (RYGB)/Atomoxetine

Vertical sleeve gastrectomy (VSG) /Atomoxetine

Roux-en-Y gastric bypass (RYGB)/Placebo

Vertical sleeve gastrectomy (VSG)/ Placebo

Arm Description

Participants with standard of care RYGB will receive atomoxetine, 0.5 mg/kg/day for 3 days

Participants with standard of care VSG will receive atomoxetine 0.5 mg/kg/day for 3 days

Participants with standard of care RYGB will receive placebo 0.5 mg/kg/day for 3 days

Participants with standard of care VSG will receive placebo 0.5 mg/kg/day for 3 days

Outcomes

Primary Outcome Measures

Orthostatic Tolerance

the time between the start of the 60 degree head up tilt until pre-syncope Participant will be placed in 60degree head-up tilt (HUT) for 30 min following by lower body negative pressure in escalating negative pressures (-20, -40, -60 mm Hg) until pre-syncope (defined as systolic BP (SBP, mm Hg) <80 or SBP>90 and pre-syncopal symptoms (nausea, lightheadedness, dizziness)

Secondary Outcome Measures

Norepinephrine transporter Inhibition

the ratio of dihydroxyphenylglycol (DHPG) to Norepinephrine is used as the biomarker for NET inhibition

Full Information

NCT ID

NCT03808740

First Posted

January 16, 2019

Last Updated

March 1, 2022

Sponsor

Vanderbilt University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03808740

Brief Title

Orthostatic Intolerance After Bariatric Surgery

Acronym

RYGB

Official Title

Orthostatic Intolerance After Bariatric Surgery

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Completed

Study Start Date

July 1, 2018 (Actual)

Primary Completion Date

May 31, 2021 (Actual)

Study Completion Date

May 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Vanderbilt University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Orthostatic Intolerance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Roux-en-Y gastric bypass (RYGB)/Atomoxetine

Arm Type

Experimental

Arm Description

Participants with standard of care RYGB will receive atomoxetine, 0.5 mg/kg/day for 3 days

Arm Title

Vertical sleeve gastrectomy (VSG) /Atomoxetine

Arm Type

Experimental

Arm Description

Participants with standard of care VSG will receive atomoxetine 0.5 mg/kg/day for 3 days

Arm Title

Roux-en-Y gastric bypass (RYGB)/Placebo

Arm Type

Placebo Comparator

Arm Description

Participants with standard of care RYGB will receive placebo 0.5 mg/kg/day for 3 days

Arm Title

Vertical sleeve gastrectomy (VSG)/ Placebo

Arm Type

Placebo Comparator

Arm Description

Participants with standard of care VSG will receive placebo 0.5 mg/kg/day for 3 days

Intervention Type

Drug

Intervention Name(s)

Atomoxetine

Other Intervention Name(s)

strattera

Intervention Description

atomoxetine 0.5 mg/kg/day.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

sugar pill

Intervention Description

sugar pill

Primary Outcome Measure Information:

Title

Orthostatic Tolerance

Description

Time Frame

about 1 hour

Secondary Outcome Measure Information:

Title

Norepinephrine transporter Inhibition

Description

the ratio of dihydroxyphenylglycol (DHPG) to Norepinephrine is used as the biomarker for NET inhibition

Time Frame

baseline and 30 minutes

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cyndya Shiabao, M.D.

Organizational Affiliation

Vanderbilt University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cyndya Shibao

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37027

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Orthostatic Intolerance After Bariatric Surgery

We'll reach out to this number within 24 hrs