Overview

The goal of this clinical trial is to evaluate the superiority of combined VLCKD, intensive lifestyle intervention and naltrexone/bupropion (N/B) versus standard of care with naltrexone/bupropion on weight loss for people with weight regain after bariatric surgery.

The main questions it aims to answer are:

Primary endpoint:

• The percentage of weight loss at 26 weeks

Secondary endpoints:

• A weight loss percentage at 10 weeks, 16 weeks and at end of trial (= 52 weeks from start)
• A proportion of patients with a weight loss percentage of 5% or more at 10, 16, 26 and 52 weeks
• A proportion of patients with a weight loss percentage of 10% or more at 10, 16, 26 and 52 weeks
• The time to reach a weight loss percentage of 5% and 10%
• The dose of naltrexone/bupropion used at 10, 16, 26 and 52 weeks and at the end of the trial
• The tolerability of VLCKD and NB
• The adherence to VLCKD and NB
• The Patient-Reported Outcome Measures (PROMs) of hunger and cravings at 0, 4, 10, 16, 26 and 52 weeks
• The change in fasting glucose, lipids and blood pressure at 10, 16, 26 and 52 weeks

Researchers will compare an experimental arm (N/B + Lifestyle + VLCKD) with comparator arm (NB + lifestyle) to see if combined VLCKD, intensive lifestyle and N/B is superior.

Participants will:

• get NB and lifestyle changes for 26 weeks
• follow a VLCKD in the first 10 weeks on top of it, if they belong to the experimental arm
• follow NB combined with lifestyle the remaining 16 weeks
• be followed-up for an extension of 26 weeks
• come to the hospital at week 1, 10, 16, 26, 52

Eligibility

Inclusion Criteria:

• Participants eligible for inclusion in this Trial must meet all of the following

  criteria

  1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
  2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner.
  3. Miminum 18 years of age at the time of Informed Consent signature
  4. Underwent bariatric surgery (RYGB or SG) with weight regain ≥10% of nadir weight
  5. People without Type 2 diabetes (T2D) • No history, no drugs, HbA1c < 6,5% and FPG <126 mg/dl) All participants that are considered for Trial participation, per the above criteria will be documented on the Screening Log, including Screen Failures.

Exclusion Criteria:

• Participants eligible for this Trial must not meet any of the following criteria:
  1. Participant has a history of type 2 diabetes mellitus (also drugs, HbA1c > 6,5% and FPG >126 mg/dl)
  2. IFemale who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
  3. Participation in an interventional Trial with an investigational medicinal product (IMP) or device
  4. Not willing to sign informed consent
  5. Younger than 18 years of age at the time of Informed Consent signature
  6. Other types of bariatric surgery other than RYGB or SG (including LAGB, BPD)
  7. Underwent bariatric surgery (RYGB or SG) with weight regain <10% of nadir weight
  8. Contraindication for VLCKD, including CKD stage 4-5, liver cirrhosis, type 1 diabetes mellitus, active gout
  9. Contraindication for NB including the use of opioids, history of CNS tumor or seizures, severe psychiatric disorder or > 2 psychotropic medications, uncontrolled hypertension
  10. Use of other drugs for weight management (e.g. GLP1Ra) in the last 3 months prior to trial intervention
  11. Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol Participants who meet one or more of the above exclusion criteria must not proceed to be enrolled/randomized in the Trial and will be identified on the Screening Log as Screen Failure.