Short Bowel Syndrome and Teduglutide Versus Placebo
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 75 |
| Updated: | 4/21/2016 |
| Start Date: | January 2014 |
| End Date: | March 2015 |
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
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.
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.
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.
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.
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.
We found this trial at
1
site
Mayo Clinic Rochester Mayo Clinic is a nonprofit worldwide leader in medical care, research and...
Click here to add this to my saved trials
