Short Bowel Syndrome and Teduglutide Versus Placebo

NCT ID: NCT02099084

Last Updated: 2016-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-03-31

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.

Conditions

Short Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Teduglutide

Intervention Type: DRUG

Participants will receive Teduglutide 0.05 mg/kg/d administered subcutaneously.

Placebo

Intervention Type: DRUG

Participants will receive placebo matching study drug, administered subcutaneously.

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.

Group Type: PLACEBO_COMPARATOR

Teduglutide

Intervention Type: DRUG

Participants will receive Teduglutide 0.05 mg/kg/d administered subcutaneously.

Placebo

Intervention Type: DRUG

Participants will receive placebo matching study drug, administered subcutaneously.

Interventions

Teduglutide

Participants will receive Teduglutide 0.05 mg/kg/d administered subcutaneously.

Intervention Type: DRUG

Placebo

Participants will receive placebo matching study drug, administered subcutaneously.

Intervention Type: DRUG

Other Intervention Names

Gattex; Revestive

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Michael Camilleri

Primary Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Camilleri, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

References

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. doi: 10.1177/0148607115597644. Epub 2015 Jul 28.

Reference Type: RESULT

PMID: 26223941 (View on PubMed)

Other Identifiers

UL1TR000135

Identifier Type: NIH

Identifier Source: secondary_id

View Link

13-004866

Identifier Type: -

Identifier Source: org_study_id