Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Short Bowel Syndrome and Teduglutide Versus Placebo

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02099084
Recruitment Status : Completed
First Posted : March 28, 2014
Results First Posted : February 22, 2016
Last Update Posted : February 22, 2016
Sponsor:
Information provided by (Responsible Party):
Michael Camilleri, Mayo Clinic

Brief Summary:

This research study was done to see what the effects are of Teduglutide on people with short bowel syndrome (SBS). Teduglutide is a synthetic medication administered as an injection, which has shown to increase intestinal blood flow, inhibit gastric secretion, increase growth of intestinal cells and increase absorption of nutrients. Teduglutide has demonstrated to decrease Total Parenteral Nutrition (TPN) requirements by 20%. Teduglutide is approved by the Food and Drug Administration (FDA) for the treatment of adult patients with Short Bowel Syndrome (SBS) who are dependent on parenteral support.

The primary hypotheses for this study were 1) that Teduglutide significantly increases the gastric emptying half time of solids when compared to placebo. 2) Teduglutide will significantly decrease the intestinal permeability and urinary excretion of lactulose when compared to placebo.


Condition or disease Intervention/treatment Phase
Short Bowel Syndrome Drug: Teduglutide Drug: Placebo Phase 4

Detailed Description:

Short bowel syndrome (SBS) refers to the anatomical and/or functional decrease in small intestinal absorptive capacity, mostly caused by extensive intestinal resections. The decrease in intestinal absorptive capacity leads to malabsorption causing malnutrition, dehydration and weight loss, all of which severely impact patient's quality of life.

In this study, qualifying participants were assigned to 2 different treatment arms consisting of placebo or Teduglutide 0.05 mg/kg subcutaneously daily for seven days. Subsequently, participants were switched over to the alternate treatment arm for seven days, after a washout period of at least seven days. In both arms, after six days of treatment or placebo, participants underwent a series of measurements during day 7 of treatment, including 8 hour GI transit, permeability measurements by using mannitol and lactulose (0-2h, 2-8h collections), and 8 hour urine and stool collections for measurement of volume. Throughout the study participants filled out a food diary and a stool diary (number, consistency, ease of passage) every day.

On day 7 of each intervention period participants arrived in the clinical research unit after having fasted for at least 8 hours. Women of childbearing potential had a pregnancy test. Participants then received their seventh dose of placebo or Teduglutide (1 dose, 1 hour before breakfast). Technetium sestamibi (99mTc) pellets were ingested in a scrambled egg, toast, and milk meal (218 kcal) to facilitate measurement of gastric transit. All subjects received a standard 550 kcal meal at 4 hours (chicken meal) after the radiolabeled meal.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Acute Effects of a Glucagon-like Peptide 2 Analog, Teduglutide, on Gastrointestinal Motor Function and Permeability in Patients With Short Bowel Syndrome on Home Parenteral Nutrition
Study Start Date : January 2014
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Teduglutide

Arm Intervention/treatment
Experimental: Teduglutide First, then Placebo
Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days, followed by a 14-day washout period, and placebo administered subcutaneously for 7 days.
Drug: Teduglutide
Participants will receive Teduglutide 0.05 mg/kg/d administered subcutaneously.
Other Names:
  • Gattex
  • Revestive

Drug: Placebo
Participants will receive placebo matching study drug, administered subcutaneously.

Placebo Comparator: Placebo First, then Teduglutide
Placebo administered subcutaneously for 7 days, followed by a 14-day washout period, and Teduglutide 0.05 mg/kg/d administered subcutaneously for 7 days.
Drug: Teduglutide
Participants will receive Teduglutide 0.05 mg/kg/d administered subcutaneously.
Other Names:
  • Gattex
  • Revestive

Drug: Placebo
Participants will receive placebo matching study drug, administered subcutaneously.




Primary Outcome Measures :
  1. Gastric Emptying Half-Time (T1/2) [ Time Frame: approximately 2 hours after radiolabeled meal is ingested ]
    The time for half of the ingested solids or liquids to leave the stomach.

  2. Overall Gut Transit [ Time Frame: baseline, approximately 6 hours after ingestion of radiolabeled meal ]
    Given the variable extent of the residual length of the small intestine and colon, the proportion emptied from the body at 6 hours was assessed as an overall estimate of the whole gut transit. The 6-hour values for intra-abdominal counts were then compared with the 100% reference values of counts (at time zero, which is immediately after ingestion of the radiolabeled meal) to determine the percentage of isotope retained in the abdomen. 100% minus the percentage of retained isotope reflected the amount emptied from the GI tract.


Secondary Outcome Measures :
  1. Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Mannitol [ Time Frame: baseline, approximately 2 hours and 8 hours after ingestion of radiolabeled meal ]
    Permeability is measured through differential excretion of urine saccharides. A sugar solution (200 mg of mannitol and 1 g lactulose in 30 mL of water) was administered with the radiolabeled test meal at visits 1 and 2. Urine was collected during 0-2 and 2-8 hours. A baseline urine sample was also collected prior to ingestion of the sugars. Chemical analysis was preformed with high-speed liquid chromatography tandem mass spectrometry.

  2. Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Lactulose at 2 Hours [ Time Frame: baseline, approximately 2 hours after ingestion of radiolabeled meal ]
    Permeability is measured through differential excretion of urine saccharides. A sugar solution (200 mg of mannitol and 1 g lactulose in 30 mL of water) was administered with the radiolabeled test meal at visits 1 and 2. Urine was collected during 0-2 and 2-8 hours. A baseline urine sample was also collected prior to ingestion of the sugars. Chemical analysis was preformed with high-speed liquid chromatography tandem mass spectrometry.

  3. Change in Small Intestinal and Colonic Permeability as Measured by Lactulose/Mannitol Ratio at 2 Hours [ Time Frame: baseline, approximately 2 hours after ingestion of radiolabeled meal ]
    Permeability is measured through differential excretion of urine saccharides. A sugar solution (200 mg of mannitol and 1 g lactulose in 30 mL of water) was administered with the radiolabeled test meal at visits 1 and 2. Urine was collected during 0-2 and 2-8 hours. A baseline urine sample was also collected prior to ingestion of the sugars. Chemical analysis was preformed with high-speed liquid chromatography tandem mass spectrometry.


Other Outcome Measures:
  1. Stool Weight at 8 Hours [ Time Frame: approximately 8 hours after ingestion of radiolabeled meal ]
    After an overnight fast, subjects received a single dose of placebo or Teduglutide 1 hour before breakfast, then consumed a radiolabeled meal. After 8 hours a stool collection was taken.

  2. Urine Volume at 8 Hours [ Time Frame: Start of the ingestion of the radiolabeled meal until 8 hours after the meal ]
    After an overnight fast, subjects received a single dose of placebo or Teduglutide 1 hour before breakfast, then consumed a radiolabeled meal. Urine was collected twice: from the start of the ingestion of the meal to 2 hours, and 2-8 hours. The total volume of urine collected was the sum of these two collections.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Short bowel syndrome
  • Dependent on parenteral nutrition

Exclusion criteria:

  • Pregnant, trying to become pregnant or lactating
  • Diabetes
  • Alcohol or drug abuse within the last year by history
  • Active Crohn's disease as evaluated by standard procedures employed by the investigator
  • History of radiation enteritis, scleroderma, celiac disease, tropical sprue, diabetes, chronic pseudo-obstruction or malignancies
  • Previous use of Teduglutide or potential allergies to Teduglutide or its constituents
  • Any hospitalization within 1 month before screening
  • Use of Octreotide, intravenous glutamine growth hormone or growth factors such as native Glucagon-like Peptide 2 (GLP-2) within the last 12 weeks
  • Infliximab or other biological agents, Azathioprine, Methotrexate, Cyclosporine, Tacrolimus, Sirolimus, should be stable for at least 8 weeks prior to baseline and remain stable during the study

    - Any investigational drug within last 30 days

  • Diuretics and oral rehydration solutions will be required to be stable for ≥4 weeks prior to baseline evaluations and remain stable during the study
  • Change in dose of antimotility or secretory agents from 2 days prior to, and throughout the two phases and washout periods of the study
  • Use of tobacco products within the prior 1 month (since nicotine can affect permeability)
  • Use of NSAIDS or aspirin within the past week
  • Use of oral corticosteroids within the previous 6 weeks
  • Ingestion of artificial sweeteners such as Splenda (sucralose), Nutrasweet (aspartame), lactulose or mannitol 2 days each of the study measurement days, e.g., foods to be avoided are sugarless gums or mints and diet soda
  • History of pancreatitis
  • Primary renal impairment (estimated glomerular filtration rate (eGFR)) <30 ml/min.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02099084


Locations
Layout table for location information
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Layout table for investigator information
Principal Investigator: Michael Camilleri, MD Mayo Clinic
Publications of Results:
Layout table for additonal information
Responsible Party: Michael Camilleri, Primary Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02099084    
Other Study ID Numbers: 13-004866
UL1TR000135 ( U.S. NIH Grant/Contract )
First Posted: March 28, 2014    Key Record Dates
Results First Posted: February 22, 2016
Last Update Posted: February 22, 2016
Last Verified: January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Short Bowel Syndrome
Syndrome
Disease
Pathologic Processes
Malabsorption Syndromes
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Postoperative Complications
Teduglutide
Gastrointestinal Agents
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs