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Obesity, MorbidPhase 4NCT04902625

Use of Mysimba in Patients With Weight Regain After Bariatric Surgery

A Phase 4 study testing Naltrexone-Bupropion Combination in people with Obesity, Morbid and Bariatric Surgery Candidate, run by Zuyderland Medisch Centrum at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Although bariatric surgery is currently the most effective treatment for morbid obesity, weight regain occurs in 16-37% of the patients (1). Weight regain is not regularly treated with antiobesity medications (AOMs). Read more about this study

Who is it for?
Ages 18 to 74 years
What is being tested?
Naltrexone-Bupropion Combination
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
116 participants
Where
1 siteNetherlands
Study dates
21 Mar 2023to Mar 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 74 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • BMI before surgery was ≥ 35,0 kg/m2
  • Patient has undergone a primary banded/non-banded Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)
  • Gaining more than 5% weight after reaching plateau phase of lowest weight

Who cannot join

  • Anatomical or surgical abnormalities for which revisional surgery is indicated.
  • Use of the following medication Monoamino-oxidase inbibitors (MAO), selective serotonin reuptake inhibitor (SSRI), Tricyclic antidepressants (TCA), haloperidol, risperidone, opioids, antiarrhythmics, betablockers, antiviral medication (HIV)
  • Pregnancy or breastfeeding
  • Patients suffering from:
  • unregulated hypertension
  • a tumour in the central nervous system
Show all 14Show fewer
  • severe liver failure
  • end stage kidney failure
  • Patients suffering from or with a history of insults
  • Patients with a history of:
  • bipolar disease
  • bulimia or anorexia nervosa
  • Patients withdrawing from alcohol or benzodiazepines
  • Patients who are not able to understand the informed consent form and patient information.

Trial locations and contacts

1 site in 1 country.

Marijn TF Jense, MD contact

088-4599719

m.jense@zuyderland.nl

Valerie M Monpellier contact

vmonpellier@obesitaskliniek.nl

Netherlands1 site, 1 recruiting
  • Zuyderland Medical Center

    Heerlen, Limburg, 6419 PC

    Marijn Jense, m.jense@zuyderland.nl

    Recruiting

Other trials in Netherlands

About this study

Although bariatric surgery is currently the most effective treatment for morbid obesity, weight regain occurs in 16-37% of the patients (1). Weight regain is not regularly treated with antiobesity medications (AOMs).

Mysimba (Contrave in US) is a AOM, it is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, and is used with lifestyle modification. Bupropion is a mild reuptake inhibitor of dopamine and norepinephrine. Naltrexone, an opioid antagonist has minimum effect on weight loss on its own. Naltrexone is thought to block the inhibitory effects of opioid receptors activated by the β-endorphin released in the hypothalamus that stimulates feeding, thus allowing the inhibitory effects of α-melanocyte stimulating hormone to reduce food intake. In patients with obesity usage of Naltrexone/Bupropion (NB) results in up to 8.2% weight loss (2). There is some evidence that also in bariatric patients with weight regain NB leads to additional weight loss (3, 4).

Read more

At the Nederlandse Obesitas Kliniek (NOK) weight regain at follow-up is currently treated with the Back on Track (BOT) program. The BOT program is an extra intervention our clinic provides for the patients who have weight regain after surgery, this is part of our standard care program.

The primary objective is to study the effect of naltrexone/bupropion in combination with the BOT module on successful weight loss(>5% weight loss) after 22 weeks in patients with weight regain after bariatric surgery, compared to the regular BOT module.

Read the detailed description

Throughout the years it has become clear that lifestyle intervention is the cornerstone for all types of bariatric treatment. Educating patients about behaviour, physical activity and intake strategies will help built a skills set, which patients can fall back on throughout their lives. Without additional lifestyle intervention a non-surgical, pharmacological or surgical treatment will be less effective. (5, 6) Besides lifestyle interventions, adjuvant pharmacological treatment has also proven to be effective in maintaining adequate weight loss. Pharmacological treatment is mostly performed in patients who are not eligible for bariatric surgery but do suffer from obesity and related comorbidities. Patients with a Body Mass Index(BMI) of ≥ 30kg/m2 or a BMI ≥ 27kg/m2 with an obesity-related comorbidity are advised to use pharmacological treatment. (7) In general the pharmacologic treatment affects appetite and therefore causes weight loss, provided that lifestyle interventions are added to the treatment.

For patients with a BMI of ≥ 40kg/m2 or a BMI ≥ 35kg/m2 with comorbid conditions bariatric surgery is advised. There is a variety of surgical treatment options, with Sleeve Gastrectomy (SG) and the Roux-en-Y gastric bypass (RYGB) being the most common. (8) An alteration of the gastro-intestinal tract is performed, which causes a change in gut hormones, bile acids and microbiota. These changes also have their effect on appetite and energy consumption causing an even higher weight reduction. (9) Although lifestyle interventions are the cornerstone of obesity treatment, bariatric surgery has proven to be a superior treatment. (9-11) Besides a positive effect on weight, bariatric surgery also has a positive effect on comorbidities, such as type 2 diabetes, hypertension, cancer incidence, cardiovascular events and cardiovascular deaths. (9, 10, 12-14) All in all we can state that bariatric surgery currently is the most effective treatment for patients suffering from morbid obesity.

Even though bariatric surgery is the most effective treatment, not all patients maintain their weight loss. As mentioned before weight regain occurs in 16-37% of the patients. (1) Currently these patients can be treated in our clinic with an extra module, the Back On Track (BOT) module. The BOT module consists of 4 extra sessions, 3 with the physiotherapist, psychologist or dietitian, and 1 with the medical doctor. During these sessions lifestyle modifications will once again be the main focus. A study performed with data from our own clinic shows an overall stabilisation of weight after this module. The regained weight will not be lost with the help of this module. Therefore other options should be explored.

One of the possibilities is the use of medication, in combination with lifestyle interventions (BOT module), to not only cause stabilisation of weight, but also weight loss at the end of our module.

Pharmacological therapy with other medication in post-bariatric patients is described to be a viable option. As described in the review performed by Sudlow et al, different medical options are being investigated. (15) At the moment most research has been focussing on pre-operative use of medication. In this review only four out of 20 studies described post-operative use of medication. Of these four only two studies researched the effect of naltrexone and bupropion combined in post-bariatric patients. Although these studies only have a small amount of participants (e.g. n=10), they do show a possible positive effect on weight loss. (3, 4, 15) Since there is a lack of research on the effect of pharmacotherapy as an addition to lifestyle interventions in post-bariatric patients, no clear guidelines can be created at the moment. (16)

Mysimba (Contrave in US) is Anti-Obesity Medication (AOM), it is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release. Naltrexone, mostly used for treatment of alcohol and opioid dependence, is thought to block the inhibitory effects of opioid receptors activated by the β-endorphin released in the hypothalamus that stimulates feeding, thus allowing the inhibitory effects of α-melanocyte stimulating hormone to reduce food intake. Bupropion is a mild reuptake inhibitor of dopamine and norepinephrine, which is used for treatment of depression and later for smoking cessation. On their own the effect on weight loss is minimal, when combined their effect on weight loss is synergistically positive. When combined with lifestyle interventions most successful results will be obtained.

In patients with obesity usage of Naltrexone/Bupropion (NB) has a stronger effect and results in up to 8.2% weight loss (2). A study performed by Apovian shows a significant difference in successful weight loss after 4 weeks, when comparing patients who use NB to patients with only lifestyle modifications. Their study had a follow-up period of 56 weeks with a extra measure timepoint at 28 weeks. All patients were measured and monitored every 4 weeks. The results at 4 weeks already showed a significant difference with the placebo group. (2) Furthermore, in a study conducted by Greenway et al after 16 weeks of follow up a significant difference in successful weight loss was observed. (17) So far not many studies have been conducted in post-bariatric patients. Even though the results thus far are scarce, they are promising. Two studies, both with a study population of 10, showed a positive result of around 5% more weight loss in post-bariatric patients. (3, 4)

In this study we will examine the effect of 2 tablets of Mysimba 8/90mg 2 times daily as addition to the Back On Track module for patients with weight regain after bariatric surgery.

Being tested
Naltrexone-Bupropion Combination
Keywords
Bariatric Surgery, Anti-obesity Medication, Weight regain
Medical subject headings
Obesity, Morbid, Medication Adherence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Naltrexone-Bupropion CombinationDrug

    Also called Mysimba, Contrave

    Naltrexone-bupropion will be added to the BOT module in the interventional arm.

Study groups in NCT04902625
Study groupRoleWhat they receive
Naltrexone-Bupropion combinationActive comparatorThe patients in this arm will receive 2 tablets of naltrexone-bupropion 8/90mg 2 times daily in combination with the Back On Track module.
Receives: Drug: Naltrexone-Bupropion Combination
ControlNo interventionThe patients is this arm will only participate in the Back On Track module and will not receive any investigational or placebo product.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effect naltrexone-bupropion in combination with the BOT module

    The primary objective is to study the effect of naltrexone/bupropion in combination with the BOT module on successful weight loss (>5% weight loss) after 22 weeks compared with the regular BOT module alone, in patients with weight regain after bariatric surgery.

    Measured: 22 weeks

Secondary outcomes (8)
  1. Persistence

    To describe the persistence of therapy of Mysimba after bariatric surgery. This will be described in amount of people completing the study with the full dosage or a lower dosage of Mysimba.

    Measured: 22 weeks

  2. Tolerated dosage

    To describe the maximal tolerated dosage

    Measured: 22 weeks

  3. Adverse effects

    To study adverse effects of the use of Mysimba

    Measured: 22 weeks

  4. Weight loss

    To monitor and compare weight loss more long term (up to 12 months) after the start of Mysimba in both study groups. Weight loss will be described in %Total weight loss.

    Measured: 12 months

  5. Eating habits

    To evaluate eating behaviour in patients with weight regain after bariatric surgery who used Mysimba compared to patients on the regular module according to the BODY-Q questionnaire

    Measured: 22 weeks

  6. Medication absorption/exposure

    1. To study bupropion and hydroxybupropion absorption/exposure by measuring steady-state serum levels in bariatric and compare these with steady-state serum levels in obese patients on Mysimba therapy who did not undergo bariatric surgery

    Measured: 16 weeks

  7. Correlate serumlevels with effectiveness

    1. to correlate bupropion and hydroxybupropion steady-state serum levels with effectiveness of Mysimba

    Measured: 16 weeks

  8. Therapeutic range

    1. to determine the therapeutic range of bupropion and hydroxybupropion plasma levels in bariatric and obese patients on Mysimba.

    Measured: 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2021
  2. Study start21 Mar 2023
  3. Primary completionMar 2025 (estimated)
  4. Study completionMar 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized controlled trail
Masking
None (open label)
Enrolment
116 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04902625
Sponsor's protocol ID
NOK0023
Status last verified
Jul 2022
First submitted
18 May 2021
Last updated
30 May 2023
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Naltrexone-Bupropion Combination in people with Obesity, Morbid and Bariatric Surgery Candidate, run by Zuyderland Medisch Centrum at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 30 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Marijn TF Jense, MD (088-4599719, m.jense@zuyderland.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect naltrexone-bupropion in combination with the BOT module (time frame: 22 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2023.

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