Liraglutide on Decreasing Parenteral Support in Short Bowel Patients (SLIPS) (SLIPS)

Pilot Study of the GLP-1 Agonist, Liraglutide, on Decreasing Parenteral Support Requirements in Short Bowel Patients.

Pilot study looking at the effect on Liraglutide in the reduction of parenteral support in patients with short bowel.

Study Overview

• Status: Withdrawn
• Conditions: Short Bowel Syndrome
• Intervention / Treatment: Drug: Liraglutide Pen Injector [Victoza]

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • St Mark's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Short bowel (≤200cm) as a result of major intestinal resection (e.g. due to injury, volvulus, vascular disease, Crohn's disease).
2. Jejunostomy patients only
3. 12 continuous months of parenteral support (PS) dependency prior to enrolment.
4. PS required at least 3 times per week to meet their caloric, fluid or electrolyte needs due to on-going malabsorption.

5. Stable PS for at least 4 consecutive weeks immediately prior to first dose of liraglutide. Stability is described as:

   1. Actual PS usage should match prescribed PS;
   2. Baseline 48-hour urine output is 1-2 L/24 hours.
6. Body mass index ≥ 19.5 kg/m2.

7. Adequate hepatic and renal function:

   1. Total bilirubin within the normal range;
   2. Alanine aminotransferase (ALT) ≤ 2.5x upper limit of normal;
   3. Serum creatinine ≤1.5x upper limit of normal.
8. Stable dosage for > 4 weeks, prior to baseline evaluations, of anti-motility and anti-diarrhoeal agents, H2 antagonists, proton pump inhibitors, bile sequestering agents and oral rehydration solutions.
9. Female subjects must be on acceptable method of contraception for a minimum of 4 weeks prior to the start of the trial; Acceptable methods of contraception would be a barrier form of contraception, oral contraceptive pill, contraceptive injection or implant or intrauterine implanted device.

Exclusion Criteria:

• Patients < 18 years of age
• Pregnancy (Female subjects who are not surgically sterile or post menopausal (defined as aged 55 years or older and/or at least 2 years have elapsed since the last menses) or who are not using medically acceptable methods of birth control during and for 30 days after the treatment period. Acceptable methods of contraception would be a barrier form of contraception, oral contraceptive pill, contraceptive injection or implant or intrauterine implanted device.
• Active malignancy
• Previous malignancy within the past 5 years
• History of multiple endocrine neoplasia type 2 (MEN 2)
• Personal history or family history of medullary thyroid cancer
• Raised serum calcitonin (a biomarker for medullary thyroid cancer) at beginning of trial period
• History of cardiac failure
• Concurrent use of diuretics
• Previous history of pancreatitis
• Recent use of other incretin based therapy in the previous 3 months
• Concurrent use of octreotide
• Type 1 or Type 2 diabetes
• Alcohol or drug abuse in last year
• > 4 hospitalisations related to short bowel or its treatment over the previous year
• Any hospitalisation 30 days prior to screening
• Introduction or dose adjustment of immunosuppressant for inflammatory bowel disease within 6 months, or treatment with biologics within the past 6 months (systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, MMF, infliximab, adalimumab, vedolizumab)
• BMI < 19 kg/m2 or > 27kg/m2 (An upper cut-off BMI of > 27kg/m2 has been chosen, as in these patients, there is often a desire to reduce BMI which will conflict with the study design by adding another variable)
• Scleroderma/radiation enteritis/coeliacs disease/refractory or tropical sprue
• Liver and renal function outside the inclusion range

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test group	Drug: Liraglutide Pen Injector [Victoza]; Pilot study of liraglutide in patients with short bowel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in parenteral support	Improvement of parenteral support on 20 weeks of Liraglutide	20 weeks post start of drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in quality of life	Improvement in Euroqol EQ5-D score. Level 1: indicating no problem, Level 5: indicating extreme problems.	20 weeks post start of drug
Duration of response	Duration of response i.e. proportion of subjects who maintain reduction in weekly PN volume from baseline at week 20.	20 weeks
Days/Nights not requiring PS	Days/Nights not requiring PS	20 weeks
Change in plasma citrulline, GLP-1, IGF-1 and PYY concentrations	Change in plasma citrulline, GLP-1, IGF-1 and PYY concentrations	20 weeks

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Siddhartha Oke, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2017
• Primary Completion (Actual): August 6, 2020
• Study Completion (Anticipated): September 30, 2020

Study Registration Dates

• First Submitted: October 25, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 12, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Liraglutide; Victoza
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Postoperative Complications; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Short Bowel Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 17IC3834

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No