Clinical trial NCT03341429: Evaluation of Liraglutide 3.0mg in Patients With Poor Weight-loss and a Suboptimal Glucagon-like Peptide-1 Response
Official title: BARI-OPTIMISE: a Double-blinded, Randomised, Placebo-controlled Trial of Liraglutide 3.0 mg in Patients With Poor Weight-loss and a Suboptimal Glucagon-like Peptide-1 Response Following Bariatric Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Keywords: obesity
GLP-1
liraglutide
diabetes
bariatric surgery
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2017-11-14
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is a double-blind, randomised, placebo-controlled, two-arm, parallel group, single-site trial
Primary purpose: TREATMENT

Brief summary: A double-blinded, randomised, placebo-controlled trial of liraglutide 3.0 mg in patients with poor weight-loss and a suboptimal glucagon-like peptide-1 response following bariatric surgery

Detailed description: Subjects with poor weight loss response (\<20% of their total weight) following 1 year or more primary gastric bypass or primary sleeve gastrectomy, will be identified from the trial site (University College London Hospital) and participant identification centre (Whittington Hospital) and invited to attend a screening visit. The screening assessment will be undertaken only upon patients providing informed consent to undergo such procedure. Information regarding medical history and concomitant medications will be gathered. In addition, full physical examination, blood test and a meal test will be performed. All female participants of childbearing potential will be tested for pregnancy. Once all data related to the screening visit has been acquired, the investigator will review the participants' eligibility for BARI-OPTIMISE trial. Patients with suboptimal GLP-1 response and fulfilling the inclusion and exclusion criteria will be invited to take part in the trial and asked to sign a second consent form. Assurance of adequate use of contraceptive throughout the trial period will be obtained before a written informed consent is sought. Consented participants will then be asked to attend a baseline visit.

During the baseline visit, data such as body weight, body composition, physical function, physical activity level and health-related quality of life will be collected. Adverse events will be reviewed and a meal test will be repeated. Upon completion of all the baseline procedures, participants will be randomised to receive either subcutaneous injection of liraglutide 3.0 mg or identical placebo for 24 weeks. Participants will be counselled for a calorie-reduced diet and to increase their level of physical activity. Participants will also be taught how to self-administer the treatment (by subcutaneous injection). For safety purpose, subject visits will be carried out at weeks 2, 4, 8, 17 and 24 of the treatment initiation. At all these visits, targeted physical examination will be performed and adverse events will be assessed. End-of-study visit will be over the phone 4 weeks after the end of treatment (i.e. week 28).

Eligibility criteria: Inclusion Criteria:

1. Patients, 1 year or more after primary RYGB or primary SG, with poor weight-loss (\<20% WL) that is not caused by either a surgical or psychological problem.
2. Adults, 18-64 years inclusive.
3. Suboptimal nutrient-stimulated GLP-1 response assessed by a meal test. Suboptimal active GLP-1 response is defined as a ≤2-fold increase in active GLP-1 circulating levels between time 0 and time 30 minutes.
4. Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control, abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.
5. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for trial treatment. NOTE: Subjects are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.
6. ≤5 % variation in body weight over preceding 3 months.
7. Fluent in English and able to understand and complete questionnaires.
8. Willing and able to provide written informed consent and comply with the trial protocol.

Exclusion Criteria:

1. Had a surgical procedure other than gastric bypass and sleeve gastrectomy.
2. Pregnant or lactating mothers.
3. Participation in other clinical intervention trial.
4. Lifetime history of suicidal behaviour or severe depression assessed by direct questioning.
5. Clinically significant medical abnormalities (e.g., unstable hypertension, clinically significant ECG abnormalities, liver cirrhosis, AST or ALT \> 3x the upper normal limit).
6. Heart rate ≥ 100 beats/minute at screening on two separate measurements.
7. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg).
8. Renal impairment (estimated glomerular infiltration rate (eGFR \<30 ml/min 1.73 m2)
9. Known or suspected hypersensitivity to liraglutide 3.0 mg and placebo or any of the excipients involved in their formulation.
10. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.
11. Personal history of pancreatitis.
12. Uncontrolled hypothyroidism or hyperthyroidism.
13. History of stroke, unstable angina, acute coronary syndrome, congestive heart failure New York Heart Association class III-IV within the preceding 12 months.
14. History of arrhythmias.
15. Inflammatory bowel disease.
16. Diabetic gastroparesis.
17. Concomitant GLP-1 receptor agonist usage.
18. Concomitant usage of medications that cause weight gain or weight loss.
19. Concomitant usage of DPPIV-inhibitors.
20. Insulin usage.

Primary outcomes:
measure: %WL
timeFrame: 24 weeks
Secondary outcomes:
measure: %fat
timeFrame: 24 weeks
measure: Skeletal muscle mass
timeFrame: 24 weeks
measure: Bone mineral density
timeFrame: 24 weeks
measure: Glucose level
timeFrame: 24 weeks
measure: Insulin
timeFrame: 24 weeks
measure: HbA1c
timeFrame: 24 weeks
measure: Leptin
timeFrame: 24 weeks
measure: Gut Hormones
timeFrame: 24 weeks
measure: Adipokines
timeFrame: 24 weeks
measure: physical functional assessment
timeFrame: 24 weeks
measure: physical function assessment
timeFrame: 24 weeks
measure: physical function assessment
timeFrame: 24 weeks
measure: physical function assessment
timeFrame: 24 weeks
measure: HRQoL
timeFrame: 24 weeks
measure: HRQoL
timeFrame: 24 weeks
measure: HRQoL
timeFrame: 24 weeks
measure: HRQoL
timeFrame: 24 weeks
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: UCLH
Study officials:
affiliation: UCL
name: Rachel L Batterham, PhD FRCP
role: PRINCIPAL_INVESTIGATOR
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