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Short Bowel Syndrome and Teduglutide Versus Placebo

Primary Purpose

Short Bowel Syndrome

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Teduglutide

Placebo

About this trial

This is an interventional treatment trial for Short Bowel Syndrome

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Teduglutide First, then Placebo

Placebo First, then Teduglutide

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Gastric Emptying Half-Time (T1/2)

The time for half of the ingested solids or liquids to leave the stomach.

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.

Secondary Outcome Measures

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.

Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Lactulose at 2 Hours

Change in Small Intestinal and Colonic Permeability as Measured by Lactulose/Mannitol Ratio at 2 Hours

Full Information

NCT ID

NCT02099084

First Posted

March 25, 2014

Last Updated

January 25, 2016

Sponsor

Mayo Clinic

1. Study Identification

Unique Protocol Identification Number

NCT02099084

Brief Title

Short Bowel Syndrome and Teduglutide Versus Placebo

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 Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Completed

Study Start Date

January 2014 (undefined)

Primary Completion Date

March 2015 (Actual)

Study Completion Date

March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Short Bowel Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

8 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Teduglutide First, then Placebo

Arm Type

Experimental

Arm Description

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.

Arm Title

Placebo First, then Teduglutide

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Teduglutide

Other Intervention Name(s)

Gattex, Revestive

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Participants will receive placebo matching study drug, administered subcutaneously.

Primary Outcome Measure Information:

Title

Gastric Emptying Half-Time (T1/2)

Description

The time for half of the ingested solids or liquids to leave the stomach.

Time Frame

approximately 2 hours after radiolabeled meal is ingested

Title

Overall Gut Transit

Description

Time Frame

baseline, approximately 6 hours after ingestion of radiolabeled meal

Secondary Outcome Measure Information:

Title

Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Mannitol

Description

Time Frame

baseline, approximately 2 hours and 8 hours after ingestion of radiolabeled meal

Title

Change in Small Intestinal and Colonic Permeability as Measured by Urinary Excretion of Lactulose at 2 Hours

Description

Time Frame

baseline, approximately 2 hours after ingestion of radiolabeled meal

Title

Change in Small Intestinal and Colonic Permeability as Measured by Lactulose/Mannitol Ratio at 2 Hours

Description

Time Frame

baseline, approximately 2 hours after ingestion of radiolabeled meal

Other Pre-specified Outcome Measures:

Title

Stool Weight at 8 Hours

Description

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.

Time Frame

approximately 8 hours after ingestion of radiolabeled meal

Title

Urine Volume at 8 Hours

Description

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.

Time Frame

Start of the ingestion of the radiolabeled meal until 8 hours after the meal

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Camilleri, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26223941

Citation

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.

Results Reference

result

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Short Bowel Syndrome and Teduglutide Versus Placebo

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