Weight Loss in Adults With Obesity Using a Combination of Low Energy Diet, Group Treatment and Intragastric Balloon

Study Overview
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Brief Summary
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In Sweden, approximately 1.3 million adults have obesity. Obesity decreases quality of life (QoL) and increases the risk of diseases such as type 2-diabetes, non-alcoholic fatty liver disease (NAFLD), cancer and cardiovascular diseases. Consequently, weight loss improves QoL and decreases the risk for obesity-related comorbidities. A treatment combination using a low energy diet (LED) and group treatment based on cognitive behavioral therapy (CBT), leads to 18 percent weight loss after 6 months. Six months treatment with an intragastric balloon (IGB) leads to 13 percent weight loss. However, both treatments are usually followed by weight regain. Combining these treatments has not been studied before but could lead to better weight maintenance. The hypothesis is that treatment of adults with obesity, with LED, CBT and IGB, leads to greater weight loss after 1 year compared to treatment with LED and CBT only. The study is a randomized, controlled clinical trial, with a 2-year follow-up. One hundred and ten adults, age 30-65 years, with a BMI of 30-45 kg/m^2 will be included. All participants will receive 6 months of LED, followed by randomization to either 6 months with IGB or a control group without IGB. All participants receive CBT-based group treatment during 12 months and followed up after 2 years. If the treatment combination of LED, CBT and IGB leads to significant weight loss and improved weight maintenance, increased QoL and reductions of comorbidities and costs of health care are expected. Effects of treatment on eating behavior, NAFLD, physical activity, psychological parameters, the gut microbiota, gut permeability and metabolomics will be assessed.

Official Title
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The Effects of a Low Energy Diet Versus Low Energy Diet and Intragastric Balloon in Adults With Obesity, All in Combination With Group Treatment: a Randomized, Controlled Trial

Conditions
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Obesity, Weight Loss, Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Dietary Supplement: Low energy diet using meal replacements
* Behavioral: CBT-based group treatment
* Device: Intragastric balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI ≥ 30 and ≤45 kg/m^2 Age 30 to 65 years Exclusion Criteria: Participation in an organized weight reduction programme or pharmacological treatment for weight loss within the last 3 months Daily use of meal replacement products within the last 3 months Previous gastric surgery Current gastric, duodenal or oesophageal ulcers Inflammatory disease of the gastrointestinal tract including oesophagitis, or specific inflammation such as Crohn's disease Known potential upper gastrointestinal bleeding conditions such as gastric or oesophageal varices Known structural abnormalities of the pharynx or oesophagus Symptoms suggestive for severe gastric motility disorder Known hiatus hernia ≥ 5 cm Cancer diagnosed within the last 5 years or ongoing treatment for cancer (except non-metastasising skin cancer) Known severe heart failure (NYHA 3-4) Known chronic obstructive pulmonary disease (FEV1 ≤ 50 percent) Kidney failure (eGFR ≤ 30 ml/min) Liver failure (liver enzymes more than 3 times the normal threshold) Known proliferative retinopathy Known or suspected abuse of alcohol or narcotics Current or history of systemic treatment with corticosteroids within the last 3 months Known myocardial infarction or stroke within the last 6 months Current or history of pancreatitis Pregnancy, intention to become pregnant or breastfeeding during the study Untreated or insufficient treated hypo- or hyperthyroidism Current use of anticoagulants: warfarin, apixaban, dabigatran, edoxaban and rivaroxaban Current use of thrombocyte aggregation inhibitors: clopidogrel and acetylsalicylic acid Known or previous eating disorder Antimicrobial treatment within 3 months prior to study may lead to postponed participation Regular consumption of probiotic capsules within 1 month prior to study start may lead to postponed participation Participants considered to be unsuitable for the study by the investigator (e.g. serious psychiatric disorders, suspected eating disorders)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study design is an open labelled, randomized, controlled clinical trial, with a ratio 1:1.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>All participants in the control group are treated with LED and CBT-based group treatment as described below. All participants (control and intervention) receive 2.5-hour sessions of CBT-based group treatment every 4 weeks for 1 year. Participants are randomly assigned to groups of 8-16 participants. Two groups of about the same size start simultaneously. The LED phase (from baseline to 24 weeks) consists of 12 weeks with 4 portions/day of liquid meal replacements, for a total of 800-880 kcal/day, followed by a 12-week slow phasing out to a regular diet. Thereafter, an energy-reduced diet (1400-1600 kcal/day) is recommended. | Dietary Supplement: Low energy diet using meal replacements<br>* The LED phase (from baseline to 24 weeks) consists of 12 weeks with 4 portions/day of liquid meal replacements, for a total of 800-880 kcal/day, followed by a 12-week slow phasing out to a regular diet. Thereafter, an energy-reduced diet (1400-1600 kcal/day) is recommended.<br>* Other names: LED;Behavioral: CBT-based group treatment<br>* All participants (control and intervention) receive 2.5-hour sessions of CBT-based group treatment every 4 weeks for 1 year. Participants are randomly assigned to groups of 8-16 participants.<br>* Other names: CBT;|
| Experimental: IGB group<br>All participants in the IGB group are treated with LED and CBT-based group treatment as described for the control group. Participants in the intervention group are treated with an IGB for 6 months from 6 months from start. | Dietary Supplement: Low energy diet using meal replacements<br>* The LED phase (from baseline to 24 weeks) consists of 12 weeks with 4 portions/day of liquid meal replacements, for a total of 800-880 kcal/day, followed by a 12-week slow phasing out to a regular diet. Thereafter, an energy-reduced diet (1400-1600 kcal/day) is recommended.<br>* Other names: LED;Behavioral: CBT-based group treatment<br>* All participants (control and intervention) receive 2.5-hour sessions of CBT-based group treatment every 4 weeks for 1 year. Participants are randomly assigned to groups of 8-16 participants.<br>* Other names: CBT;Device: Intragastric balloon<br>* An IGB (Orbera IGB, Apollo Endosurgery Inc., Austin, Texas, (CE certified)) is set in place endoscopically by a gastroenterologist at Örebro University Hospital, Region Örebro county, and is left in the stomach for 6 months. A proton-pump inhibitor is prescribed to counteract an increased risk to develop a gastric ulcer. During the first 2 weeks, dietary adjustments are necessary to adapt to the IGB. Thereafter, an energy-reduced diet (1400-1600 kcal/day) is recommended identical to the control group. The IGB is removed endoscopically after 6 months IGB treatment.<br>* Other names: IGB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss in percent of total body weight | Total body weight is measured in light indoor clothing without shoes on a calibrated bio-impedance scale. | Change from baseline at 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight loss in percent of total body weight | Total body weight is measured in light indoor clothing without shoes on a calibrated bio-impedance scale. | Change from baseline at 6 months | 
| Weight loss in percent of total body weight at 2-year follow-up | Two years after treatment start and thus one year after completion of the intervention, participants will be followed up on total body weight. Weight is measured in light indoor clothing without shoes on a calibrated bio-impedance scale. | Change from baseline at 24 months | 
| The proportion of participants with ≥5 percent reduction of total body weight from baseline | Total body weight is measured in light indoor clothing without shoes on a calibrated bio-impedance scale. | 6, 12 and 24 months | 
| The proportion of participants with ≥10 percent reduction of total body weight from baseline | Total body weight is measured in light indoor clothing without shoes on a calibrated bio-impedance scale. | 6, 12 and 24 months | 
| The proportion of participants with ≥15 percent reduction of total body weight from baseline | Total body weight is measured in light indoor clothing without shoes on a calibrated bio-impedance scale. | 6, 12 and 24 months | 
| Effect of treatment on bioelectrical impedance measurement to assess fat mass | Bioelectrical impedance analysis is performed with a Body Composition Analyzer BC-420MA. Fatt mass is estimated and results are presented in kilograms. | Change from baseline at 6, 12 and 24 months | 
| Effect of treatment on bioelectrical impedance measurement to assess muscle mass | Bioelectrical impedance analysis is performed with a Body Composition Analyzer BC-420MA. Muscle mass is estimated and results are presented in kilograms. | Change from baseline at 6, 12 and 24 months | 
| Change in waist circumference | Waist circumference is measured in centimeters according to the World Health Organization protocol. | Change from baseline at 6, 12 and 24 months | 
| Change in 2-hour oral glucose tolerance test | Effect on the 2-hour oral glucose tolerance test (OGTT) is measured by analysing glucose (mmol/L) in a fasting blood sample. Thereafter the participant drinks a standardized amount of glucose. After 120 minutes, a blood sample is analyzed again for glucose (mmol/L) . | Change from baseline at 6 and 12 months | 
| Change in Hemoglobin A1c | Hemoglobin A1c (HbA1c) in mmol/L is analyzed in a fasting blood sample. | Change from baseline at 6 and 12 months | 
| Change in serum lipids | Total cholesterol, HDL, LDL and triglycerides are analyzed in a fasting blood sample. Results are presented in mmol/L. | Change from baseline at 6 and 12 months | 
| Change in insulin | Insulin is analyzed in a fasting blood sample and presented in mIE/L. | Change from baseline at 6 and 12 months | 
| Change in Homeostatic Model Assessment of Insulin Resistance | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) is calculated using fasting values of insulin and glucose. | Change from baseline at 6 and 12 months | 
| Change in kidney function | Kidney function is assessed by analysing blood samples for creatinine (µmol/L). The result is used to calculate the estimated glomerular filtration rate (eGFR) using the Lund-Malmö revised calculation. eGFR is presented as mL/min/1,73m^2. | Change from baseline at 6 and 12 months | 
| Change in liver transaminases | Liver transaminases are measured by analysing alanine transaminase (ALT) and aspartate transaminase (AST) in a fasting blood sample. Data is presented in µkat/L. | Change from baseline at 6 and 12 months | 
| Change in thrombocytes | Thrombocytes are analyzed in a fasting blood sample and presented as 10*9/L. | Change from baseline at 6 and 12 months | 
| Change in blood pressure | Blood pressure is measured using a correct cuff size for the circumference of participant's arm after 5 minutes rest in a sitting position. | Change from baseline at 6 and 12 months | 
| Effect of treatment on vibration-controlled transient elastography measurement to assess level of liver steatosis and fibrosis | Evaluation of NAFLD at baseline and effect of treatment using vibration-controlled transient elastography to detect liver stiffness (in kPa) and determine the steatosis and fibrosis score (0 to 4 there 0 means no steatosis or fibrosis). | Change from baseline at 6 and 12 months | 
| Effect of treatment on RAND-36 (SF-36) to measure QoL | RAND-36 (SF-36) questionnaire is validated to measure QoL and comprises 36 items measuring eight domains that reflect a wide spectrum of physical and mental health aspects: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. | Change from baseline at 6, 12 and 24 months | 
| Effect of treatment on the Obesity-related Problems scale, version 3 (OPv3) to measure weight-related psychosocial functioning | OPv3 is validated to measure obesity-specific quality of life with 26 items. OP measures the negative effects of obesity on psychosocial functioning. | Change from baseline at 4, 12, 20, 24, 28, 36, 44, 52 and 104 weeks | 
| Effects of treatment on the Three-Factor Eating Questionnaire-Revised 18 (TFEQ-R18V2) items to measure eating behavior | The TFEQ-R18V2 is a validated questionnaire to measure three aspects of eating behavior: uncontrolled eating (9 items), cognitive restraint (3 items), and emotional eating (6 items). | Change from baseline at 4, 12, 20, 24, 28, 36, 44, 52 and 104 weeks | 
| Effects of treatment on hunger and satiety | Hunger and satiety are assessed by a questionnaire with 9 single items on a 5-point Likert scale. | Change from baseline at 4, 12, 20, 24, 28, 36, 44, 52 and 104 weeks | 
| Effect of treatment on 7-day step count to measure physical activity | Step count is measured during 7 consecutive days using an accelerometer. The data is completed with questions on water-based activities and cycling on these days. | Change from baseline at 6, 12 and 24 months | 
| Effect of treatment on sitting time and physical activity | Self-reported data on physical activity will be measured by a validated questionnaire from the National Board of Health and Welfare, Sweden, concerning sitting time and hours of light and moderate activity. | Change from baseline at 6, 12 and 24 months | 
| Effect of treatment on the use of medication for glucose lowering treatment, hypertension and hyperlipidemia | Effect of treatment on the use of medication for glucose lowering treatment, hypertension and hyperlipidemia is assessed by asking participants at every study contact, if changes in medication have been made. A patient record survey for prescribed medication is performed at 12 and 24 months. | Change from baseline at 6, 12 and 24 months | 
| The effect of treatment on the use of health care and absence from work during treatment | Health care utilization and absence from work are measured with self-assessment questionnaires. A patient record survey is performed at 12 and 24 months. | Change from baseline at 6, 12 and 24 months | 
| Calculation of cost-effectiveness of treatment using multi-variable analysis | Cost-effectiveness is analyzed using data on health care utilization, absence from work, use of medication and QoL questionnaires (RAND-36 and OPv3). Data is combined and analyzed together to calculate and report cost-effectiveness. All used measurements are also described above as separate secondary outcome measures. | Change from baseline at 6, 12 and 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity, Weight loss, Low energy diet, Intragastric balloon, Group treatment, Non-alcoholic fatty liver disease, Quality of life, Body weight, Glucose metabolism, Eating behavior, Microbiomics, Physical activity, Gastrointestinal symptoms, Psychological parameters