Weight Loss Strategies for Obesity

(FGB Trial)

Recruiting at 2 trial locations

Overseen By Beth Henk

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Must not be taking: Hormone replacement therapy

Disqualifiers: Tobacco use, Pregnancy, Organ dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 4-6 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how different diets and surgeries affect metabolism in adults with obesity. It compares low-carbohydrate meals to standard ones and studies their interaction with the body before and after weight loss. Participants will either follow a very low-calorie diet or undergo Roux-en-Y gastric bypass surgery. This trial suits individuals who have experienced obesity for a while, are scheduled for this specific surgery, or are interested in trying a low-calorie diet, and do not have Type 2 Diabetes. Participants will assist researchers in determining which method might be more effective for managing obesity. As an unphased trial, this study provides a unique opportunity to contribute to foundational research that could shape future obesity treatments.

Do I need to stop my current medications for this trial?

Yes, you may need to stop taking medications that could affect metabolic function, as determined by the investigator.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Roux-en-Y gastric bypass (RYGB) surgery can lead to significant weight loss and improve conditions like type 2 diabetes. Studies indicate that patients may lose up to 31.8% of their body weight within the first 18 months after surgery. However, this surgery carries some risks, with reports suggesting higher complication rates compared to other procedures. Considering these risks is important when evaluating this option.

For the very low-calorie diet (LCD), specific safety data is not available from the sources. This diet involves consuming significantly fewer calories than usual to aid weight loss. While it can be effective, some individuals might experience side effects such as tiredness or dizziness. Since this trial is not in a defined phase, the safety evidence is limited, and individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for obesity because they offer distinct approaches to weight loss. Roux-en-Y gastric bypass surgery is unique because it physically alters the digestive system to limit how much food you can eat by creating a small pouch from the stomach. This mechanical change can lead to significant and long-lasting weight loss. On the other hand, a very low-calorie diet is a non-surgical option that focuses on drastically reducing calorie intake to achieve similar weight loss goals. This diet requires commitment but can be effective for individuals looking to avoid surgery. Both treatments aim for a similar result but provide different pathways to achieving weight loss, giving patients and healthcare providers more options tailored to individual needs and preferences.

What evidence suggests that this trial's treatments could be effective for obesity?

Research has shown that Roux-en-Y gastric bypass (RYGB) surgery, one of the treatments in this trial, can lead to significant and lasting weight loss. Studies indicate that about 72% of patients maintain at least a 20% weight loss even after 10 years. RYGB also improves conditions like type 2 diabetes, which affects blood sugar management.

Participants in the very low-calorie diet (LCD) arm of this trial can expect weight loss by significantly reducing calorie intake. Although specific long-term data for LCD in this trial is not available, it generally supports weight loss through strict dieting. Both RYGB and LCD in this trial aim to improve overall health and reduce obesity-related problems. ^{2 6 7 8 9}

Who Is on the Research Team?

Samuel Klein, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for men and women with obesity, having a BMI of 35-55 kg/m², who are scheduled for RYGB surgery or will follow a very low-calorie diet (VLCD), but do not have Type 2 Diabetes. Participants should not be pregnant, breastfeeding, using tobacco products regularly, exercising more than 90 minutes per week, or have had hormone replacement therapy in the last six months.

Inclusion Criteria

I have a BMI between 35-55 and do not have Type 2 Diabetes.

I am scheduled for RYGB surgery, my BMI is between 35-55, and I do not have Type 2 Diabetes.

Exclusion Criteria

VLCD Group: Exercise ≥90 minutes per week

I am not on medication that affects my metabolism.

I am not on medication that affects metabolism, as per my doctor's opinion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either a low-calorie diet intervention or Roux-en-Y gastric bypass surgery to achieve ~16-18% weight loss

4-6 months

Multiple visits for meal consumption and assessments

Post-Intervention Assessment

Metabolic responses to low-carbohydrate and standard-carbohydrate meals are evaluated, including insulin kinetics, glucose kinetics, and other metabolic parameters

1-2 weeks

2 visits (in-person) for meal consumption and sample collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Roux-en-Y gastric bypass surgery
• Very low-calorie diet

Trial Overview The study investigates how Roux-en-Y gastric bypass (RYGB) surgery versus a very low-calorie diet affects levels of FGF21—a hormone that may help regulate post-meal nutrient balance and improve symptoms of diabetes and obesity. It also examines the impact on glucose, insulin, triglyceride metabolism as well as fat and muscle tissue function.

How Is the Trial Designed?

Group I: RYGB group Experimental Treatment 1 Intervention

Subjects in this group are scheduled to undergo Roux-en-Y gastric bypass surgery and will be assessed after \~16-18% weight-loss

Group II: LCD Group Active Control 1 Intervention

Subjects in this group will participate in a low-calorie diet intervention to achieve \~16-18% weight loss.

Roux-en-Y gastric bypass surgery is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Roux-en-Y gastric bypass for:

• Type 2 Diabetes
• Obesity

Approved in European Union as Roux-en-Y gastric bypass for:

• Type 2 Diabetes
• Obesity

Approved in Canada as Roux-en-Y gastric bypass for:

• Type 2 Diabetes
• Obesity

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Kilo Diabetes & Vascular Research Foundation

Collaborator

Trials

1

Recruited

30+

National Center for Advancing Translational Science (NCATS)

Collaborator

Trials

100

Recruited

32,100+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

In a study of 375 patients who underwent Roux-en-Y gastric bypass (RYGB), those who had banded RYGB experienced significantly greater weight loss (32.6% vs 27.6% at 5 years) compared to those with non-banded RYGB, indicating that banding may enhance long-term weight loss outcomes.

Both banded and non-banded RYGB had similar complication rates and did not show significant differences in the improvement or remission of comorbidities, suggesting that the banded approach is a safer option for achieving better weight loss without increasing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Benefits of Banded over Non-banded Roux-en-Y Gastric Bypass in Patients with Morbid Obesity: a Multi-center Study. Jense, MTF., Palm-Meinders, IH., Sigterman-Nelissen, R., et al.[2022]

Surgery, particularly Roux-en-Y gastric bypass (RYGB) and bilio-pancreatic diversion (BPD), is highly effective for significant weight loss in patients with severe obesity, but these procedures can lead to specific micronutrient deficiencies that require early supplementation.

Complications from these surgeries can result in severe malnutrition, highlighting the importance of understanding the anatomical and physiological changes post-surgery to manage nutritional needs effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing the obese patient after bariatric surgery: a case report of severe malnutrition and review of the literature. Kushner, R.[2017]

In a study of 1426 obese patients who underwent Roux-en-Y gastric bypass (RYGB), 17.1% experienced significant weight regain (≥15% of their 1-year postoperative weight) after an average of 6 years post-surgery.

Younger age was identified as a significant predictor of weight regain, even when accounting for the time elapsed since surgery, highlighting the need for further research into the factors influencing weight loss and regain after RYGB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of weight regain in patients who underwent Roux-en-Y gastric bypass surgery. Shantavasinkul, PC., Omotosho, P., Corsino, L., et al.[2022]

In a study of 213 type 2 diabetes patients with a BMI of 25 to 32.5 kg/m2, Roux-en-Y gastric bypass (RYGB) was found to be more effective than medical treatment in achieving significant metabolic improvements, with 23.9% of RYGB patients meeting the triple endpoint compared to only 7.0% in the medical group.

However, RYGB was associated with a higher rate of complications (36 vs. 22), highlighting the need to weigh the benefits of improved metabolic outcomes against the risks of surgical complications when considering treatment options for patients with lower BMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year outcomes of Roux-en-Y gastric bypass vs medical treatment in type 2 diabetes with a body mass index lower than 32.5 kg/m2: a multicenter propensity score-matched analysis. Ling, J., Tang, H., Meng, H., et al.[2022]

In a study of 313 morbidly obese patients who underwent Roux-en-Y gastric bypass (RYGB), the length of the biliopancreatic limb (BPL) and alimentary limb (AL) did not significantly affect %excess weight loss (%EWL) after 12 months.

However, after 36 months, patients with a longer BPL experienced a significantly higher %EWL compared to those with a shorter BPL, suggesting that BPL length may play a role in long-term weight loss outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of alimentary and biliopancreatic limb length in outcomes of Roux-en-Y gastric bypass. Darabi, S., Pazouki, A., Hosseini-Baharanchi, FS., et al.[2022]

In a study analyzing serum samples from 21 patients who regained weight after Roux-en-Y gastric bypass (RYGB) and 14 patients who maintained weight loss, a distinct metabolomic fingerprint was found in those with weight regain, primarily involving amino acid and one-carbon metabolism.

The findings suggest that specific serum metabolites, particularly those related to serine, glycine, and threonine pathways, could potentially serve as biomarkers to predict which patients are at risk of weight regain after RYGB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Metabolomic Signatures in Patients with Weight Regain and Sustained Weight Loss After Gastric Bypass Surgery: A Pilot Study. Abidi, W., Nestoridi, E., Feldman, H., et al.[2021]

In a study of 85 adolescents who underwent Roux-en-Y gastric bypass (RYGB), adherence to prescribed micronutrient supplementation was only 44-61% over 5 years, leading to significant long-term deficiencies, particularly in iron and vitamin D.

Adolescents who did not adhere to supplementation had lower levels of essential nutrients and a higher prevalence of anemia and deficiencies, highlighting the need for ongoing monitoring and potentially increased supplementation post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Micronutrient intake and biochemistry in adolescents adherent or nonadherent to supplements 5 years after Roux-en-Y gastric bypass surgery. Henfridsson, P., Laurenius, A., Wallengren, O., et al.[2020]

In a study of 32 obese patients who underwent conversion from Roux-en-Y gastric bypass (RYGB) to duodenal switch (DS), the patients achieved a mean excess weight loss (EWL) of 56.4% by 24 months post-surgery, indicating the effectiveness of this revision procedure.

The study found no significant difference in weight loss outcomes between two types of DS procedures (RYDS and single anastomosis DS), suggesting that both methods are equally effective for patients seeking further weight loss after failed RYGB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mid-term outcomes of gastric bypass weight loss failure to duodenal switch. Surve, A., Zaveri, H., Cottam, D., et al.[2022]

Roux-en-Y gastric bypass (RYGB) is a highly effective bariatric surgery option, especially for patients experiencing treatment failure from other procedures, with up to 20% of RYGB patients facing complications that may require revision.

Recent advancements in endoscopic techniques provide less invasive alternatives for addressing complications and failures from bariatric surgeries, such as transoral outlet reduction and endoscopic suturing, which can help manage issues like gastroesophageal reflux and hypoglycemic episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FROM COMPLEX EVOLVING TO SIMPLE: CURRENT REVISIONAL AND ENDOSCOPIC PROCEDURES FOLLOWING BARIATRIC SURGERY. Zorron, R., Galvão-Neto, MP., Campos, J., et al.[2022]

In a study of 1,009 patients with class II and III obesity, those who underwent Roux-en-Y gastric bypass (RYGB) surgery within one year had a significantly lower risk of major adverse cardiovascular events (MACE) compared to those who were medically managed, with an adjusted hazard ratio of 0.62.

RYGB surgery also resulted in lower mortality rates (adjusted HR of 0.51), indicating its potential effectiveness in improving long-term health outcomes for obese patients, although it did not significantly reduce the occurrence of new-onset atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Long-Term Impact of Bariatric Surgery on Development of Atrial Fibrillation and Cardiovascular Events in Obese Patients: An Historical Cohort Study. Yuan, H., Medina-Inojosa, JR., Lopez-Jimenez, F., et al.[2021]

Roux-en-Y gastric bypass (RYGB) is a safe and effective bariatric surgery for achieving long-term weight loss in obese Chinese patients with a BMI under 35 kg/m2, with 37% of patients maintaining significant weight loss after 5 years.

Early weight loss, specifically a total body weight loss of 24.39% at 6 months, is a strong predictor of successful weight maintenance at 5 years, indicating that monitoring early outcomes can help assess long-term success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss at six months is the surrogate of long-term treatment outcomes for obese Chinese with a BMI less than 35 kg/m2 undergoing Roux-en-Y gastric bypass. Du, D., Wang, L., Chen, W., et al.[2022]

After Roux-en-Y gastric bypass (RYGB) surgery, patients showed a significant shift in food preferences from high-energy foods (like high-fat/sweet) to low-energy foods (like low-energy/savory), which was linked to changes in brain activity in areas responsible for food processing.

The study found that neural responses to high-energy food cues decreased after surgery, while plasma levels of the endocannabinoid anandamide increased, suggesting that RYGB may alter brain mechanisms that influence food preferences, although changes in appetite-related hormones like ghrelin did not correlate with these neural changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altered neural responsivity to food cues in relation to food preferences, but not appetite-related hormone concentrations after RYGB-surgery. Zoon, HFA., de Bruijn, SEM., Smeets, PAM., et al.[2018]

Roux-en-Y gastric bypass (RYGB) leads to significant hormonal changes, such as increased fasting PYY and GLP-1 levels, which are associated with greater weight loss compared to laparoscopic adjustable gastric banding (LAGB).

RYGB not only reduces sweet cravings but also maintains lower ghrelin levels over time, suggesting that these hormonal adaptations contribute to improved insulin sensitivity and enhanced weight loss efficacy compared to LAGB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Modulation of Appetitive Hormones and Sweet Cravings After Adjustable Gastric Banding and Roux-en-Y Gastric Bypass. Tsouristakis, AI., Febres, G., McMahon, DJ., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40709782/

Evaluating the Effectiveness and Long-term Outcomes of ... Results: RYGB was associated with more significant long-term weight loss and superior T2DM remission rates. SG had a lower risk of nutritional ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1700459

Weight and Metabolic Outcomes 12 Years after Gastric ... Furthermore, at 10 years, 72% of the patients who had undergone Roux-en-Y gastric bypass had maintained at least a 20% weight loss from baseline ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12380876/

Laparoscopic Roux-en-Y Gastric Bypass: Evolution of ... RYGB is an efficient MBS procedure, associated with sustained weight loss and improvement of metabolic complications; a slight worsening occurs ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2819400

Ten-Year Outcomes Following Roux-en-Y Gastric Bypass ... Total weight loss was 20.0% (95% CI, 15.3%-24.7%) for RYGB and 33.9% (95% CI, 27.8%-40.0%) for DS (P = .001). Mean serum lipid levels, except ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0039606024001818

Comprehensive outcomes after Roux-en-Y gastric bypass ... The maximum mean percentage total weight loss achieved at 1 year was 31.5% ± 5.7% and was consistently >20% throughout follow-up. Sustained resolution of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3819407/

Clinical factors associated with weight loss outcomes after ... Roux-en-Y gastric bypass (RYGB) surgery can induce a substantial weight loss that is associated with improvement in type 2 diabetes, decreased incidence of ...

7. asmbs.org asmbs.org/news_releases/new-study-shows-long-term-effectiveness-of-gastric-bypass-in-treating-type-2-diabetes-and-obesity/

New Study Shows Long-term Effectiveness of Gastric ... Peak weight loss of 31.8% was achieved after 18 months and stabilized at 23% after 10 years and up to the 20-year mark. The overall 15-year ...

8. jamanetwork.com jamanetwork.com/journals/jamasurgery/fullarticle/2795683

Safety and Effectiveness of Gastric Bypass and Sleeve ... Many publications, including those from the PCORnet Bariatric Study, have shown higher rates of complications with RYGB when compared with SG.

9. nature.com nature.com/articles/s41598-024-82200-5

Outcomes and complications after long versus short ... Both long and short-pouch gastric bypass surgeries are effective and safe for weight loss and remission of obesity-associated medical problems in patients with ...