Semaglutide 2.4 mg in Patients With Poor Weight-loss (BARI-STEP)

BARI-STEP:A Double-blinded, Randomised, Placebo-controlled Trial of Semaglutide 2.4 mg in Patients With Poor Weight-loss Following Bariatric Surgery.

A double-blinded, randomised, placebo-controlled trial of semaglutide 3.0 mg/ml in patients with poor weight-loss following bariatric surgery. The primary aim of this trial is to determine whether, and the extent to which, 68 weeks of subcutaneous semaglutide 3.0 mg/ml causes greater percentage weight loss (%WL), reduction in adiposity, improvement in metabolic and inflammatory indices and health-related quality of life (HRQoL) than placebo, in patients with poor weight loss following gastric bypass or sleeve gastrectomy.

Study Overview

• Status: Active, not recruiting
• Conditions: Obesity; Diabetes; Metabolic Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Semaglutide 3 mg

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rachel L Batterham; Phone Number: 02076790991; Email: r.batterham@ucl.ac.uk
• Study Contact Backup: Name: Alanna Brown; Phone Number: 02076796308; Email: alanna.brown@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, WC1E 6JF
    • Janine Makaronids

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients, ≥1 year primary GB or primary SG, with poor weight-loss (<20% WL) that is not caused by either a surgical or psychological problem.
2. Adults, 18-65 years inclusive.
3. Females of childbearing potential and female partners of male participants must be willing to use highly effective method of contraception (hormonal or barrier method of birth control; abstinence) (Appendix 2) from the time consent is signed until 2 months after treatment discontinuation.
4. Females of childbearing potential must have a negative pregnancy test within 7 days prior to randomisation. 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.
5. A self-reported ≤5 % variation in body weight over preceding 3 months.
6. Fluent in English and able to understand and complete questionnaires.
7. Participants capable to provide written informed consent and comply with the trial protocol.

Exclusion Criteria:

1. Bariatric surgical procedure other than GB and SG, or revision bariatric surgery of any operation type.
2. Personal history of type I diabetes or type II diabetes mellitus currently treated with insulin.
3. Concomitant use of GLP-1R agonist or DPPIV-inhibitors.
4. Female who is pregnant, breast-feeding, or intends to become pregnant.
5. Current participation in other clinical intervention trial.
6. History of suicidal attempt in the previous 5 years or untreated severe depression or mental health condition assessed by direct questioning.
7. Symptomatic gallstone disease
8. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg).
9. Renal impairment measured as glomerular infiltration rate (eGFR <15 ml/min 1.73 m2
10. Known or suspected hypersensitivity to semaglutide or any of the excipients involved in their formulation.
11. Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.
12. History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
13. Personal history of acute pancreatitis 180 days before screening or chronic pancreatitis.
14. Uncontrolled thyroid disease.
15. History of stroke, unstable angina, acute coronary syndrome, congestive heart failure New York Heart Association class III-IV within the preceding 12 months.
16. Untreated clinically significant arrhythmias.
17. Diabetic gastroparesis.
18. Concomitant usage of medications that cause weight gain or weight loss.
19. Known or suspected abuse of alcohol or recreational drugs.
20. Severe hepatic impairment diagnosed via liver function blood tests and clinical evaluation
21. Any additional factor, which in the investigator's opinion, might jeopardise the subject's safety or compliance with the trial protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Semaglutide 2.4mg/week subcutaneous injection for 68 weeks. The treatment includes an initial 16-week escalation phase followed by 52 weeks of treatment at study dose, i.e., 2.4mg/week.	Drug: Semaglutide 3 mg; Semaglutide 2.4 mg/week, subcutaneous injection. Treatment dose: 16 weeks of dose escalation + 52 weeks of study dose (i.e., 2.4 mg/week).
Placebo Comparator: Control; Placebo administration, once weekly, subcutaneous injection.	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss	Percentage of total weight loss	68 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
body weight reduction ≥10%	To compare the percentage of participants receiving subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo who after 68 weeks achieve a body weight reduction ≥10%	68 weeks
body weight reduction ≥15%	To compare the percentage of participants receiving subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo who after 68 weeks achieve a body weight reduction ≥15%	68 weeks
body weight reduction ≥20%	To compare the percentage of participants receiving subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo who after 68 weeks achieve a body weight reduction ≥20%	68 weeks
Change in circulating HbA1c levels	The effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon HbA1c	68 weeks
Change in circulating HbA1c levels in participants with pre-diabetes at baseline	The effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon HbA1c in participants with pre-diabetes at baseline	68 weeks
Change in circulating HbA1c levels in participants with T2D at baseline	The effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon HbA1c in participants with diabetes at baseline	68 weeks
Systolic and diastolic BP	The effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon BP	68 weeks
Systolic and diastolic BP in participants with pre-existing hypertension	The effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon BP in participants with pre-existing hypertension	68 weeks
pharmacological agents required for the management of hypertension	The number of pharmacological agents required for the management of hypertension in participants with pre-existing hypertension	68 weeks
Change in circulating lipids	To compare the effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon circulating lipids	68 weeks
Change in circulating HsCRP and inflammatory cytokines	To compare the effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon inflammatory markers	68 weeks
Changes in food craving scores assessed through power of food questionnaire	To compare the effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon food cravings	68 weeks
Changes in HRQoL	To compare the effect of 68 weeks of subcutaneous semaglutide 3.0 mg/ml at a dose of 2.4mg per week versus placebo administration upon HRQoL	68 weeks
GLP-1 levels	To investigate the relationship between fasted and meal-stimulated active GLP-1 levels at baseline and %WL at 68 weeks	68 weeks

Collaborators and Investigators

• Sponsor: University College, London

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 28, 2021
• First Posted (Actual): October 12, 2021

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 6, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: diabetes; obesity; semaglutide
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Body Weight; Insulin Resistance; Hyperinsulinism; Body Weight Changes; Metabolic Syndrome; Weight Loss
• Other Study ID Numbers: 142522

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