Orthostatic Intolerance After Bariatric Surgery

NCT ID: NCT03808740

Last Updated: 2024-09-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-01
• Study Completion Date: 2021-05-31

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.

Conditions

Orthostatic Intolerance

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

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

Group Type: EXPERIMENTAL

Atomoxetine

Intervention Type: DRUG

atomoxetine 0.5 mg/kg/day.

Vertical sleeve gastrectomy (VSG) /Atomoxetine

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

Group Type: EXPERIMENTAL

Atomoxetine

Intervention Type: DRUG

atomoxetine 0.5 mg/kg/day.

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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

sugar pill

Vertical sleeve gastrectomy (VSG)/ Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

sugar pill

Interventions

Atomoxetine

atomoxetine 0.5 mg/kg/day.

Intervention Type: DRUG

Placebo

sugar pill

Intervention Type: DRUG

Other Intervention Names

strattera; sugar pill

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Cyndya Shibao, MD

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cyndya Shiabao, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Cyndya Shibao

Nashville, Tennessee, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

180499

Identifier Type: -

Identifier Source: org_study_id