Short Bowel Syndrome and Teduglutide Versus Placebo

Short Bowel Syndrome Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02099084
• Other study ID #: 13-004866
• Secondary ID: UL1TR000135
• Status: Completed
• Phase: Phase 4
• First received: March 25, 2014
• Last updated: January 25, 2016
• Start date: January 2014
• Est. completion date: March 2015

Study information

• Verified date: January 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Short Bowel Syndrome
• Syndrome

Intervention

Drug:
• Teduglutide
Participants will receive Teduglutide 0.05 mg/kg/d administered subcutaneously.
• Placebo
Participants will receive placebo matching study drug, administered subcutaneously.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Wi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Stool Weight at 8 Hours	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.	approximately 8 hours after ingestion of radiolabeled meal	No
Other	Urine Volume at 8 Hours	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.	Start of the ingestion of the radiolabeled meal until 8 hours after the meal	No
Primary	Gastric Emptying Half-Time (T1/2)	The time for half of the ingested solids or liquids to leave the stomach.	approximately 2 hours after radiolabeled meal is ingested	No
Primary	Overall Gut Transit	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.	baseline, approximately 6 hours after ingestion of radiolabeled meal	No
Secondary	Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Mannitol	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.	baseline, approximately 2 hours and 8 hours after ingestion of radiolabeled meal	No
Secondary	Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Lactulose at 2 Hours	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.	baseline, approximately 2 hours after ingestion of radiolabeled meal	No
Secondary	Change in Small Intestinal and Colonic Permeability as Measured by Lactulose/Mannitol Ratio at 2 Hours	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.	baseline, approximately 2 hours after ingestion of radiolabeled meal	No