NCT02204813

Brief Summary

There is a marked and long-lasting improvement in glucose homeostasis that follows Roux-en-y gastric bypass surgery (RYGB) in humans. This improvement has been attributed in large part to an intestinal hormone, called GLP-1, that is released into the circulation immediately after eating. The purpose of this study is to determine if GLP-1 mediates the beneficial effects of RYGB surgery on glucose homeostasis in humans.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
13

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jul 2014

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2014

Completed
27 days until next milestone

First Submitted

Initial submission to the registry

July 28, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 30, 2014

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 17, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 17, 2015

Completed
Last Updated

April 27, 2018

Status Verified

April 1, 2018

Enrollment Period

1.4 years

First QC Date

July 28, 2014

Last Update Submit

April 25, 2018

Conditions

Bypass, GastricRoux-en-Y Gastric BypassVertical Sleeve GastrectomyGastric BandingBariatric Surgery

Keywords

Gastric BypassRYGBGLP-1XeninInsulin SecretionGlucose HomeostasisVertical SleeveLap Band

Outcome Measures

Primary Outcomes (1)

  • Insulin secretion rates (ISRs) during each treatment

    ISRs will be measured at various times before and after ingestion of a liquid mixed meal.

    5.5 hours

Secondary Outcomes (5)

  • Plasma glucose levels during each treatment.

    5.5 hours

  • Plasma glucagon levels during each treatment.

    5.5 hours

  • Plasma GLP-1 during each treatment.

    5.5 hours

  • Plasma C-peptide levels during each treatment.

    5.5 hours

  • The rate of gastric emptying during each treatment.

    5.5 hours

Study Arms (1)

Post RYGB Surgery

EXPERIMENTAL

Healthy, weight stable individuals, with previous Roux-en-Y gastric bypass surgery. No clinical evidence of type 2 diabetes before and after surgery. Each participant will receive placebo or the indicated doses of xenin-25.

Drug: PlaceboDrug: Lo-XeninDrug: Hi-XeninDrug: Extra Hi-Xenin

Interventions

PlaceboDRUG

A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes. Starting at minus 15 minutes, an intravenous infusion of albumin alone (placebo) will be administered for 5.25 hours.

Also known as: Control, Albumin Alone
Post RYGB Surgery
Lo-XeninDRUG

A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes. Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 4 pmoles/kg/min will be administered for 5.25 hours.

Also known as: Lo-Xen
Post RYGB Surgery
Hi-XeninDRUG

A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes. Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 12 pmoles/kg/min will be administered for 5.25 hours.

Also known as: Hi-Xen
Post RYGB Surgery
Extra Hi-XeninDRUG

A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes. Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 24 pmoles/kg/min will be administered for 5.25 hours.

Also known as: XHi-Xen
Post RYGB Surgery

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Individuals must be able to consent for their own participation (no mental impairment affecting cognition or willingness to follow study instructions).
  • Healthy, weight stable, with previous Roux-en-Y gastric bypass surgery and no clinical evidence of type 2 diabetes either before and after Roux-en-Y gastric bypass surgery.
  • Women of childbearing potential must be currently taking/using a method of birth control that is acceptable to the investigators. A pregnancy test will be done at the beginning of each visit. Any woman with a positive pregnancy test will be removed from the study.
  • Willingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be made to complete this visit during study participation.)

You may not qualify if:

  • Lacks cognitive ability to sign the consent \&/or follow the study directions for themselves.
  • Women unwilling to comply with using an acceptable method of contraception during the course of the study, or who are currently breast-feeding.
  • Volunteers with a history of Acute Pancreatitis.
  • Volunteers with a history of cancer (except for skin cancer).
  • Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic pancreatitis including hypertriglyceridemia (triglycerides \>400mg/ml) hypercalcemia (blood calcium level \>11.md/dl) and/or the presence of gallstones.
  • Subjects taking medications known to affect glucose tolerance.
  • Hematocrit from the lab is below 33% (or if the finger stick hemoglobin measured with the HemoCue 201+ is \<11.2 g/dl).
  • Any major medical conditions, or conditions that in the opinion of the PI make the subject unsuitable for the study.
  • Subjects with abnormal kidney function as measured by the Creatinine concentration will be excluded.
  • Subjects with a history of active liver disease or AST/ALT levels \>2X upper limit of normal will also be excluded.
  • Total Bilirubin levels should be \<2.
  • Subjects unwilling to allow the use of their own blood or albumin in the preparation of the peptides. (The blood will prevent sticking of the peptide to the tubing; an alternative method has been sought but not found.)
  • Unwillingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be made to complete this visit during study participation.)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

  • Sterl K, Wang S, Oestricker L, Wallendorf MJ, Patterson BW, Reeds DN, Wice BM. Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery. Peptides. 2016 Aug;82:76-84. doi: 10.1016/j.peptides.2016.06.001. Epub 2016 Jun 7.

    PMID: 27288245RESULT

MeSH Terms

Interventions

Albumins

Intervention Hierarchy (Ancestors)

ProteinsAmino Acids, Peptides, and Proteins

Study Officials

  • Burton M Wice, PhD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

  • Dominic Reeds, MD

    Washington University School of Medicine

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Model Details: Patients with prior RYGB surgery receive all interventions, each on a separate day.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 28, 2014

First Posted

July 30, 2014

Study Start

July 1, 2014

Primary Completion

November 17, 2015

Study Completion

November 17, 2015

Last Updated

April 27, 2018

Record last verified: 2018-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)