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Orthostatic Intolerance After Bariatric Surgery (RYGB)

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ClinicalTrials.gov Identifier: NCT03808740
Recruitment Status : Recruiting
First Posted : January 18, 2019
Last Update Posted : January 24, 2019
Sponsor:
Information provided by (Responsible Party):
Cyndya Shibao, Vanderbilt University Medical Center

Tracking Information
First Submitted Date  ICMJE January 16, 2019
First Posted Date  ICMJE January 18, 2019
Last Update Posted Date January 24, 2019
Actual Study Start Date  ICMJE July 1, 2018
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
Orthostatic Tolerance [ Time Frame: about 1 hour ]
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)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03808740 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
Norepinephrine transporter Inhibition [ Time Frame: baseline and 30 minutes ]
the ratio of dihydroxyphenylglycol (DHPG) to Norepinephrine is used as the biomarker for NET inhibition
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Orthostatic Intolerance After Bariatric Surgery
Official Title  ICMJE Orthostatic Intolerance After Bariatric Surgery
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.

Furthermore, 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Orthostatic Intolerance
Intervention  ICMJE
  • Drug: Atomoxetine
    atomoxetine 0.5 mg/kg/day.
    Other Name: strattera
  • Drug: Placebo
    atomoxetine 0.5 mg/kg/day.
Study Arms  ICMJE
  • 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
    Intervention: Drug: Atomoxetine
  • Experimental: Vertical sleeve gastrectomy (VSG) /Atomoxetine
    Participants with standard of care VSG will receive atomoxetine 0.5 mg/kg/day for 3 days
    Intervention: Drug: Atomoxetine
  • 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
    Intervention: Drug: Placebo
  • Placebo Comparator: Vertical sleeve gastrectomy (VSG)/ Placebo
    Participants with standard of care VSG will receive placebo 0.5 mg/kg/day for 3 days
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 16, 2019)
45
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2020
Estimated Primary Completion Date June 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cyndya Shibao, M.D. 615-936-4584 cyndya.shibao@vumc.org
Contact: Shea Scudder, BSN 615-322-7568 shea.k.scudder@vumc.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03808740
Other Study ID Numbers  ICMJE 180499
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Cyndya Shibao, Vanderbilt University Medical Center
Study Sponsor  ICMJE Vanderbilt University Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Cyndya Shiabao, M.D. Vanderbilt University Medical Center
PRS Account Vanderbilt University Medical Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP