Orthostatic Intolerance After Bariatric Surgery

Orthostatic Intolerance Clinical Trial

— RYGB  

Official title:

Orthostatic Intolerance After Bariatric Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03808740
• Other study ID #: 180499
• Status: Completed
• Phase: Phase 1
• Start date: July 1, 2018
• Est. completion date: May 31, 2021

Study information

• Verified date: March 2022
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: May 31, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Orthostatic Intolerance

Intervention

Drug:
• Atomoxetine
atomoxetine 0.5 mg/kg/day.
• Placebo
sugar pill

Locations

Country	Name	City	State
United States	Cyndya Shibao	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	about 1 hour
Secondary	Norepinephrine transporter Inhibition	the ratio of dihydroxyphenylglycol (DHPG) to Norepinephrine is used as the biomarker for NET inhibition	baseline and 30 minutes