Cardiometabolic Syndrome, Obesity and Cardiovascular Risk, Overweight , Obesity
Conditions
Keywords
Obesity Class I, Hypertension, Hyperlipidemia, Prediabetes
Brief summary
The increasing prevalence of obesity, its serious health consequences, and the substantial economic burden on healthcare systems underscore a pressing need for effective, long-term prevention strategies that can be implemented in primary care. Emerging evidence suggests that combining lifestyle modification with dietary supplements and pharmacological treatment may enhance and prolong intervention effects, yet comparative long-term data on their individual and combined efficacy are limited. Therefore, this study aims to evaluate the independent and additional effects of a comprehensive lifestyle intervention, a mushroom-based dietary supplement, and bupropion treatment over 12 months, to identify more effective and sustainable strategies for obesity prevention in overweight and obese adults.
Detailed description
This is a 12-month, multicenter, randomized, parallel-group, open-label, controlled trial investigating the effects of lifestyle changes, lyophilized powder from edible mushrooms, and bupropion treatment on adiposity and cardiometabolic risk in people with overweight. The study includes five parallel treatment arms: 1.Control; 2. Lifestyle; 3. Lifestyle + Dietary supplement; 4. Lifestyle + Pharmacological treatment; 5.Lifestyle + Dietary supplement + Pharmacological treatment. 250 subjects will be enrolled and randomized in five parallel groups with 50 subjects in each treatment arm. Randomization will be performed in four strata, defined by sex (male or female) and cardiometabolic risk factors (presence or absence of hypertension, hyperlipidemia, or prediabetes). The randomization for each stratum will be done within balanced blocks to ensure approximately equal numbers of subjects across the treatment arms within each stratum. The study population will be composed such that each level of the stratification factors is represented by at least 30% of participants, i.e., at least 30% men and 30% women, and at least 30% with and 30% without cardiometabolic risk factors. Participants in treatment arm 4 and 5 receiving the pharmacological treatment will undergo re-randomization after 6 months (visit 4) in a 1:1 ratio to either discontinue the medication or continue at a maintenance dose. The study comprises eight physical visits: enrolment visit (Visit 1), randomization visit (Visit 2), four follow-up visits conducted during the treatment period (Visit 3-6), and two follow-up visits conducted after the treatment period at 24 and 36 months after inclusion in the study (Visits 8, and 9). In addition, one follow-up assessment will be conducted via telephone 18 months after inclusion (Visit 7). Long-term follow-up of the participants will be performed through national registers. Such data may be obtained for five years before and up to 20 years after inclusion in the study and will be assessed in relation to baseline data and data collected during the physical visits and telephone follow-up.
Interventions
DRUGBupropion 150 mg
Bupropion sustained-release (SR) tablets will be administered for a total of either 6 or 12 months. Treatment will begin at 150 mg once daily for one week to optimize tolerability. If well tolerated, the dose will be increased to 150 mg twice daily (morning and early afternoon) as the target maintenance dose, until 6 months into the intervention period (visit 4). At visit 4, participants will be re-randomized to either discontinue the treatment, or continue at a maintenance dose of 150 mg daily, for the remainder of the intervention. Dose adjustments, temporary or, if necessary, permanent discontinuation will be permitted for participants experiencing adverse effects, including neuropsychiatric symptoms, insomnia, or clinically significant increases in blood pressure or heart rate
DIETARY_SUPPLEMENTLyophilized powder from edible mushrooms
The lyophilized powder will consist of a mixture from two edible mushroom species: Hericium erinaceus and Pleurotus ostreatus. Participants randomized to the treatment arms receiving the lyophilized powder from edible mushrooms will be instructed to consume it as part of their daily diet. The lyophilized powder can be incorporated into an optional number of meals, at a weekly dose of 60 grams.
BEHAVIORALLifestyle Management
The lifestyle intervention will be based on the healthy Nordic diet and increased physical activity. In addition, the intervention will include other behavioral changes related to health, such as stress management, better sleep, and mindfulness. Behavioral change support will be given through digital self-help content on a study-specific website as well as physical and digital group session.
Sponsors
Uppsala University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Men and women aged 18-55 years. * BMI of 25.0 - 34.9 kg/m2. * Signed informed consent. * Have a mobile phone, tablet, or computer with internet access. * Cardiometabolic risk factors: a) None of the following diagnoses: hypertension, hyperlipidemia, or prediabetes according to WHO classification (Stratum A); b) One or several of the following diagnoses: hypertension, hyperlipidemia, or prediabetes according to WHO classification (Stratum B). * For women of childbearing potential: use of a highly effective birth control method
Exclusion criteria
* Present food intolerances and/or allergies of relevance to the interventions, such as celiac disease and allergy to edible mushrooms or fungal spores. * Contraindication to bupropion, or any unacceptable risk with either treatment as assessed by the investigator. Specifically, and not covered elsewhere: 1. History of epilepsy or lowered seizure threshold; 2. History of bulimia or anorexia nervosa; 3. Central nervous system tumor; 4. Hypersensitivity to bupropion; 5. History of bipolar disorder; 6. Known or suspected Brugada syndrome; * Current or recent adherence to a low-calorie diet, receipt of pharmacological treatment for weight loss, and/or weight loss of \> 3 kg within the past 3 months. * Previous or planned bariatric surgery * Diagnosed diabetes, coronary heart disease, heart failure, stroke, liver failure or kidney disease (eGFR\<60 ml/min/1.73m2) as well as other ongoing serious conditions with short life expectancy or conditions affecting participation in the study. * Any condition, as judged by the investigator, that suggests that the participant will be non-compliant or otherwise unsuitable to study medication or study participation. For example, serious psychiatric, eating, alcohol or substance abuse disorders. * Use of the following medications within indicated time frames: 1. Other bupropion-containing products (last 2 weeks); 2. Other weight lowering-drugs: orlistat, phentermine-topiramate, sodium-glucose transporter 2 inhibitors (SGLT2i), GLP-1 receptor agonists (last 3 months); 3. Antipsychotics, mirtazapine, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (last 3 months); 4. MAOIs (last 2 weeks); 5. Systemic glucocorticoids (last 3 months); 6. Testosterone, anabolic steroids (last 6 months); 7. Medications not listed above that are metabolized by CYP2D6; 8. Medications that affect CYP2B6; * Be pregnant or intend to become pregnant during the study period. * Involvement in the planning and/or conduct of the study. * Ongoing participation in another interventional clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in body weight | 6 months after randomization | Percent change in body weight. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically meaningful change in body weight | 6 months after randomization | Proportion of participants achieving ≥5% reduction in body weight. |
| Status of the composite of obesity and cardiometabolic risk conditions | 6 months after randomization | Participants will be classified into ordered categories based on obesity status (body mass index \[BMI\] ≥30 kg/m² vs \<30 kg/m²) and number of cardiometabolic risk conditions (central adiposity, hypertension, hyperlipidemia, prediabetes/type 2 diabetes), forming a composite ordinal outcome analyzed using proportional odds models. |
Countries
Sweden
Contacts
CONTACTMartin Lundqvist, MD, PhD
PRINCIPAL_INVESTIGATORMartin Lundqvist, MD, PhD
Uppsala University
STUDY_CHAIRJan Eriksson, MD, PhD
Uppsala University
Outcome results
None listed