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Short Bowel Syndrome and Teduglutide Versus Placebo

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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

Tracking Information
First Submitted Date  ICMJE March 25, 2014
First Posted Date  ICMJE March 28, 2014
Results First Submitted Date  ICMJE January 25, 2016
Results First Posted Date  ICMJE February 22, 2016
Last Update Posted Date February 22, 2016
Study Start Date  ICMJE January 2014
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2016)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 25, 2014)
Change in gastrointestinal transit and measurement of intestinal permeability to lactulose with Teduglutide compared to placebo. [ Time Frame: Post 7 day treatment in both arms with a 14 day washout period between both treatment arms. ]
To measure gastrointestinal transit of solids and intestinal permeability to lactulose in patients with short bowel syndrome (SBS) before and after the administration of Teduglutide compared to placebo.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2016)
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2014)
Measurement of intestinal permeability to mannitol with Teduglutide compared to placebo. [ Time Frame: Post 7 day treatment in both arms with a 14 day washout period between both treatment arms. ]
To measure intestinal permeability to mannitol and in patients with short bowel syndrome before and after administration of Teduglutide compared to placebo.
Current Other Pre-specified Outcome Measures
 (submitted: January 25, 2016)
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures
 (submitted: March 25, 2014)
  • To measure stool weight and urine volume in patients with SBS after administration of Teduglutide compared to placebo. [ Time Frame: 7 days post treatment with Teduglutide compared to placebo, participants will collect stool weight and urine volume for 8 hours. ]
    To measure stool weight and urine volume after the administration of Teduglutide or placebo.
  • Measurement of serum lipopolysaccharide (LPS) with Teduglutide compared to placebo. [ Time Frame: 7 days post treatment with Teduglutide compared to placebo, participants will have serum lipopolysaccharide (LPS) drawn 2 hours after meal ingestion. ]
    To measure serum lipopolysaccharide (LPS) 2 hours after meal ingestion in both arms of treatment.
 
Descriptive Information
Brief Title  ICMJE Short Bowel Syndrome and Teduglutide Versus Placebo
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Short Bowel Syndrome
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Teduglutide
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: Teduglutide
    • Drug: Placebo
Publications * Iturrino J, Camilleri M, Acosta A, O'Neill J, Burton D, Edakkanambeth Varayil J, Carlson PJ, Zinsmeister AR, Hurt R. Acute Effects of a Glucagon-Like Peptide 2 Analogue, Teduglutide, on Gastrointestinal Motor Function and Permeability in Adult Patients With Short Bowel Syndrome on Home Parenteral Nutrition. JPEN J Parenter Enteral Nutr. 2016 Nov;40(8):1089-1095. Epub 2015 Jul 28.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: March 25, 2014)
8
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02099084
Other Study ID Numbers  ICMJE 13-004866
UL1TR000135 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michael Camilleri, Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael Camilleri, MD Mayo Clinic
PRS Account Mayo Clinic
Verification Date January 2016

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