Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control group | Active Comparator | 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. |
|
| IGB group | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low energy diet using meal replacements | Dietary Supplement | 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. |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of the calculated risk for liver fibrosis using the fibrosis-4 (FIB-4) calculation to prevalence of liver fibrosis in the study population detected by vibration-controlled transient elastography | The risk for liver fibrosis is calculated using the FIB-4 calculation (ALT, AST, thrombocytes and age) and compared with results of vibration-controlled transient elastography on prevalence of liver steatosis and fibrosis. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Marije Galavazi, PhD, MD | Contact | +46196026631 | marije.galavazi@regionorebrolan.se | |
| Johan Jendle, Professor | Contact | +46709571257 | johan.jendle@oru.se |
| Name | Affiliation | Role |
|---|---|---|
| Johan Jendle, Professor | johan.jendle@oru.se | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medicinmottagning 5/Överviktsenheten, University Hospital Örebro | Recruiting | Örebro | 70185 | Sweden |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The study design is an open labelled, randomized, controlled clinical trial, with a ratio 1:1.
Not provided
Not provided
Not provided
Not provided
|
|
| CBT-based group treatment | Behavioral | 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. |
|
|
| Intragastric balloon | Device | 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. |
|
|
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 |
| At baseline, 6 and 12 |
| Effect of treatment on lipidomics | Evaluation of NAFLD by analysing lipidomic signatures using mass spectrometry based lipidomics. | Change from baseline at 6 and 12 months |
| Change in gut microbiota compositions during treatment with LED, re-introduction of the recommended diet and treatment with IGB | Stool samples are taken and will be analyzed for quantitative and qualitative microbial composition by using next generation metagenomic sequencing. | Change from baseline at 2, 4, 6, 9 and 12 months |
| Food frequency questionnaires to evaluate change in dietary intake | Food frequency questionnaires (FFQ) will be used to assess dietary intake. This is a common way to evaluate eating habits and, in this way, evaluation of the gut microbiota composition in relation to dietary patterns is possible to assess. | Change from baseline, 6 and 12 months |
| The Bristol Stool Form Scale is used to asses stool form | The Bristol Stool Form Scale (BSFS) is used to asses stool form at the same time points as the collection of stool samples. The scale shows 7 pictures of different forms of stool, from watery diarrhea to compact. Participants are asked to choose the most frequent form of stool they have had the past week. | Change from baseline at 2, 4, 6, 9 and 12 months |
| Change in Glucagon-like peptide-1 | Glucagon-like peptide-1 (GLP-1) is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in Glucagon-like peptide-2 | Glucagon-like peptide-2 (GLP-2) is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in peptide YY | Peptide YY (PYY) is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in leptin | Leptin is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in ghrelin | Ghrelin is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in pro-insulin | Pro-insulin is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in C-peptide | C-peptide is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in glucagon | Glucagon is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in adiponectin | Adiponectin is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in glycerol | Glycerol is analysed in a fasting blood sample. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of hormonal parameters in the coming years. | Change from baseline at 6 and 12 months |
| Change in free fatty acid | Free fatty acid (FFA) is analysed in a fasting blood sample. | Change from baseline at 6 and 12 months |
| Effect of treatment on highly sensitive C-reactive protein | Highly sensitive C-reactive protein (hs-CRP) is analysed in mg/L as a measure for inflammation. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of inflammatory parameters in the coming years. | Change from baseline at 6 and 12 months |
| Effect of treatment on Interleukin-6 | Interleukin-6 (IL-6) is analysed as a measure for inflammation. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of inflammatory parameters in the coming years. | Change from baseline at 6 and 12 months |
| Effect of treatment on Tumor Necrosis Factor-alfa | Tumor Necrosis Factor-alfa (TNF-alfa) is analysed as a measure for inflammation. tumor necrosis factor (TNF)-alfa, and Plasminogen activator inhibitor-1 (PAI-1). Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of inflammatory parameters in the coming years. | Change from baseline at 6 and 12 months |
| Effect of treatment on Plasminogen Activator Inhibitor-1 | Plasminogen activator inhibitor-1 (PAI-1) is analysed as a measure for inflammation. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of inflammatory parameters in the coming years. | Change from baseline at 6 and 12 months |
| Effect of treatment on metabolomics | Changes in metabolomics are assessed by mass spectrometry based approaches for global analysis of molecular lipids (lipidomics) and polar metabolites. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of metabolic parameters in the coming years. | Change from baseline at 6 and 12 months |
| Effect of treatment on Zonulin | Zonulin is analysed in a fasting blood sample as a measure for gut permeability. Extra plasma and serum will be collected in a biobank to be able to make use of expected new developed and validated analysis of gut permeability in the coming years. | Change from baseline at 6 and 12 months |
| Gastrointestinal Symptom Rating Scale to assess gastrointestinal symptoms | The Gastrointestinal Symptom Rating Scale (GSRS) is an instrument with 15-items validated to assess gastro-intestinal (GI) symptoms associated with GI disorders. It contains 5 subscales (Reflux, Diarrhea, Constipation, Abdominal Pain, and Indigestion Syndrome). The scores per subscale range from 1 to 7. Higher scores represent more discomfort. | Baseline, 4, 12, 20, 24, 28, 36, 44 and 52 weeks |
| Visceral Sensitivity Index to assess fear of gastrointestinal symptoms | The Visceral Sensitivity Index (VSI) measures GI symptom-specific anxiety and comprises 15 items. | Baseline, 4, 12, 20, 24, 28, 36, 44 and 52 weeks |
| Nepean Dyspepsia Index to assess dyspepsia | The Short form-Nepean dyspepsia index measures upper GI symptoms with 10 items. | Baseline, 4, 12, 20, 24, 28, 36, 44 and 52 weeks |
| Rome IV criteria to assess symptoms for irritable bowel syndrome | Rome IV is a diagnostic questionnaire for functional GI disorders, and comprises of 89 items in a flowchart. | Baseline, 6 and 12 months |
| 13C Spirulina Breath test to assess gastric emptying rate in participants randomized to IGB treatment | Gastric emptying rate is measured prior to IGB placement in participants randomized to IGB. Gastric emptying rate will be measured using the FDA-approved non-invasive, non-radioactive 13C Spirulina Breath test (Cairn Diagnostics, Brentwood, Tennessee, USA). | 1 to 28 days before IGB placement |
| Analysis of number and causes of early extractions of the gastric balloon to asses tolerability of IGB treatment | The number of participants in need of an early extraction of the IGB, thus prior to 6 months treatment, is assessed. The cause for early removal is assessed. Specifically, possible causes for intolerability are assessed by combining data on gastric-emptying, the need for early extraction of the IGB (within 6 months), gastro-intestinal symptoms using 4 questionnaires (GSRS, Rome-IV, VSI and Nepean) and two QoL questionnaires (RAND-36 and OP). All these parameters are also described as separate outcome measures. | 24, 28, 36, 44 and 52 weeks |
| Change in Depression Module (PHQ-9) questionnaire | PHQ-9 is used to assess effect of psychological parameters on treatment results and tolerability. To analyze effect of psychological parameters on treatment results, data analyses will combine this data with treatment effect on weight, gastrointestinal symptoms and QoL. | Change from baseline at 4, 12, 20, 24, 28, 36, 44 and 52 weeks |
| Change in Anxiety module (GAD-7) questionnaire | GAD-7 is used to assess effect of psychological parameters on treatment results and tolerability. To analyze effect of psychological parameters on treatment results, data analyses will combine this data with treatment effect on weight, gastrointestinal symptoms and QoL. | Change from baseline at 4, 12, 20, 24, 28, 36, 44 and 52 weeks |
| Change in Somatic symptom severity ('somatization') module (PHQ-15) questionnaire | PHQ-15 is used to assess effect of psychological parameters on treatment results and tolerability.To analyze effect of psychological parameters on treatment results, data analyses will combine this data with treatment effect on weight, gastrointestinal symptoms and QoL. | Change from baseline at 6 and 12 months |
| Pittsburgh Sleep Quality Index to assess sleep quality | Change in sleep quality is assessed using the Pittsburgh Sleep Quality Index (PSQI). | Change from baseline at 4, 12, 20, 24, 28, 36, 44 and 52 weeks |
| Acceptance and Action Questionnaire for Weight-Related Difficulties | Acceptance and Action Questionnaire for Weight-Related Difficulties (AAQ-W) measures experimental and psychological inflexibility in relation to weight-related feelings, thoughts and actions. | Change from baseline at 4, 12, 20, 24, 28, 36, 44 and 52 weeks |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D015431 | Weight Loss |
| D065626 | Non-alcoholic Fatty Liver Disease |
| D001835 | Body Weight |
| D005247 | Feeding Behavior |
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001836 | Body Weight Changes |
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001522 | Behavior, Animal |
| D001519 | Behavior |
Not provided
Not provided