Prolonged Daily Fasting for Obesity

Overseen By Lisa Chow, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must not be taking: Beta-blockers, Weight-affecting drugs

Disqualifiers: Diabetes, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to manage obesity by testing different eating patterns. Participants will join groups to try either Time Restricted Eating (eating only during an 8-hour window), Caloric Restriction (a weight loss diet involving reduced overall intake), or continue their usual eating habits. It targets individuals with a Body Mass Index (BMI) of 30 to 55 who have maintained a stable weight for at least three months and can track their eating using a smartphone app. The goal is to identify more effective weight loss strategies beyond simply reducing calorie intake. As an unphased trial, this study provides a unique opportunity to contribute to innovative research on weight management strategies.

Will I have to stop taking my current medications?

The trial requires that you do not use certain medications that affect weight, such as beta-blockers, insulin, and others. If you are on these medications, you may need to stop them to participate.

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

Research has shown that both time-restricted eating (TRE) and calorie reduction (CR) are generally safe and well-tolerated methods for managing obesity. TRE involves eating only during a specific time each day, such as an 8-hour window, and has been found to aid weight loss and improve health without affecting muscle mass. No major negative effects have been widely reported.

For CR, which involves consuming fewer calories than usual, some studies have noted possible side effects like difficulty concentrating or remembering things. However, it remains an effective way to lose weight and address health issues related to obesity. Overall, both methods have been studied and show promise in safely managing obesity. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these investigational approaches to obesity because they offer unique lifestyle-based alternatives to traditional methods like medication and surgery. Time Restricted Eating (TRE) limits eating to an 8-hour window, potentially simplifying weight management by naturally reducing calorie intake without strict dietary rules. Caloric Restriction (CR) focuses on reducing daily caloric intake by 15%, similar to long-term studies like CALERIE-2, but aims for more immediate results through a structured plan. Both methods utilize a mobile app for tracking, making them more accessible and easier to adhere to compared to conventional treatments.

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

This trial will compare Time Restricted Eating (TRE) and Caloric Restriction (CR) for weight loss in individuals with obesity. Studies have shown that TRE, where individuals eat only during an 8-hour period each day, can result in a 3%–5% weight loss over 2–12 months. TRE also lowers fasting insulin levels without muscle loss, which is important for overall health. Meanwhile, research has indicated that eating 15% fewer calories, known as CR, is also effective, leading to about a 15% weight loss in some cases. Both methods have been proven to aid weight loss and improve health in people with obesity. While TRE focuses on when individuals eat, CR focuses on how much they eat, and both offer benefits. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with obesity (BMI between 30 and 55) who have had a stable weight for the past three months, use a smartphone, wake up early, get average sleep, and have an eating window of over 14 hours. It's not for shift workers, pregnant individuals, those with certain medical conditions or abnormal lab results, history of eating disorders or using specific medications.

Inclusion Criteria

Own a smartphone compatible with the myCircadianClock (mCC) phone application

Eating window (time between 1st food intake and last food take) ≥14 hours using mCC

Self-reported habitual wakening between 5-9 am

Exclusion Criteria

Concern for active eating disorder per screening questionnaire

Illiteracy

MRI contraindication (metal in body, claustrophobia)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either Time Restricted Eating (TRE) or Caloric Restriction (CR) for weight and body composition evaluation

12 weeks

Weekly dietitian reviews

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Caloric Restriction
• Time Restricted Eating

Trial Overview The study is testing if prolonged daily fasting can be as effective as traditional calorie cutting in helping obese people manage their weight. Participants will either follow Time Restricted Eating (TRE) where they eat during limited hours or Caloric Restriction (CR), reducing overall food intake.

How Is the Trial Designed?

Group I: Time Restricted Eating (TRE) Experimental Treatment 1 Intervention

For the TRE group, we will restrict the eating window to 8 hours, where they will eat ad libitum. This is the same interval established by Dr. Panda and by our preliminary data. This interval will be entered into the mCC app and participants will be asked to adhere to this eating window during the intervention. All eating occasions will be logged using the mCC app. Only water and medications will be allowed outside of the eating window.

Group II: Caloric Restriction (CR) Active Control 1 Intervention

Participants randomized to CR will meet with the study dietitian prior to the intervention and be counseled on options to reduce their caloric intake by 15%, while maintaining their eating window. The 15% reduction was selected as our preliminary data and recent literature suggest that TRE with ad libitum intake reduces caloric intake by \~270 to 300 cal/day. The 15% CR is similar to the 11.9% CR achieved by the CALERIE-2 study, which is a 2 year study of CR.26 All eating occasions will be logged using the mCC app. The weekly dietitian review of the mCC information will include maintenance of the eating window and examination of dietary intake to determine compliance with the 15% CR.

Group III: Unrestricted Eating (non-TRE) Active Control 1 Intervention

For the unrestricted eating (non-TRE) group, participants will eat ad libitum per their usual habits. They will receive initial counseling about mCC logging. All eating occasions will be logged using the mCC app.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In an 8-week study with 59 obese participants, alternate day fasting (ADF) led to a significant weight loss of 4.2%, while only a small percentage reported mild adverse effects like constipation and dizziness.

ADF was associated with improvements in eating disorder symptoms, including a decrease in depression and binge eating, suggesting that it may have beneficial effects on body image and eating behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of alternate day fasting and effect on disordered eating behaviors. Hoddy, KK., Kroeger, CM., Trepanowski, JF., et al.[2018]

In a study of 43 insulin-resistant adults over 12 months, both alternate-day fasting (ADF) and daily calorie restriction (CR) led to similar weight loss, with ADF resulting in an 8% reduction and CR a 6% reduction in body weight.

ADF was more effective than CR in significantly lowering fasting insulin levels and insulin resistance, with reductions of 52% and 53% respectively, compared to only 14% and 17% for CR, indicating ADF may be a better option for improving glucoregulatory factors in insulin-resistant individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Effects of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance. Gabel, K., Kroeger, CM., Trepanowski, JF., et al.[2020]

Intermittent energy restriction (IER) strategies, such as intermittent fasting and time-restricted feeding, show similar effectiveness in weight loss compared to continuous energy restriction (CER) in adults with obesity, based on a review of randomized trials lasting at least 8 weeks.

Out of 11 studies analyzed, 9 found no significant differences in weight or body fat loss between IER and CER, suggesting that IER can be a viable alternative for obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Rynders, CA., Thomas, EA., Zaman, A., et al.[2021]

Time-restricted eating (TRE) is a promising dietary strategy that can help improve metabolic health and restore circadian rhythms, potentially aiding in the prevention and treatment of obesity and its complications.

Current evidence from previous TRE trials suggests a need for more extensive clinical research, including large-scale controlled trials, to fully understand the efficacy and mechanisms of TRE in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Research progress on the application of time-restricted eating in adult obesity and related metabolic diseases]. He, JH., Sun, CY., Liang, C.[2022]

In a 10-week study with 16 obese participants, alternate day modified fasting (ADMF) led to an average weight loss of 5.6 kg, demonstrating its effectiveness as a weight loss strategy.

Participants adapted well to ADMF, with significant reductions in energy intake on fasting days and no increase in hunger, while maintaining physical activity levels, suggesting that dietary and activity adaptations contribute to the weight loss observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary and physical activity adaptations to alternate day modified fasting: implications for optimal weight loss. Klempel, MC., Bhutani, S., Fitzgibbon, M., et al.[2021]

Alternate-day fasting (ADF) is a safe and well-tolerated weight loss method, with 93% of participants completing the 8-week study without adverse effects.

While ADF and a standard caloric restriction diet produced similar weight loss results after 8 weeks, ADF showed more favorable changes in body composition, particularly in fat and lean mass, during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Catenacci, VA., Pan, Z., Ostendorf, D., et al.[2019]

Intermittent energy restriction (IER) was found to be a feasible and effective weight management strategy for adolescents aged 12-17 with obesity, leading to a significant reduction in BMI %95th percentile after 12 weeks (-5.6%) and maintained reductions at 26 weeks.

Participants reported IER as easy and pleasant to follow, indicating high acceptability, and the intervention also resulted in improvements in cardiovascular health markers, such as reduced carotid intima-media thickness and improved flow-mediated dilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent Energy Restriction Is a Feasible, Effective, and Acceptable Intervention to Treat Adolescents with Obesity. Jebeile, H., Gow, ML., Lister, NB., et al.[2023]

Intermittent fasting (IF) may be an effective weight management strategy for overweight and obese adults, but its evidence base in humans is still limited, with only one published systematic review available.

Current guidelines from the National Institute for Health and Care Excellence (NICE) do not recommend very low calorie diets (VLCD) as a routine treatment for obesity, highlighting concerns about potential side effects and the sustainability of fasting approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intermittent fasting interventions for the treatment of overweight and obesity in adults aged 18 years and over: a systematic review protocol. Jane, L., Atkinson, G., Jaime, V., et al.[2022]

In a pilot study involving 40 abdominally obese participants, time-restricted feeding (TRF) led to a significant reduction in waist circumference by an average of 5.3 cm and improved blood sugar levels, as indicated by a decrease in HbA1c by 1.4 mmol/mol after three months.

TRF was well-adopted by participants, who achieved their fasting goals on 85.5% of recorded days, suggesting that this lifestyle modification could be an effective and easy-to-implement strategy for reducing abdominal obesity and lowering the risk of related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to Time-Restricted Feeding and Impact on Abdominal Obesity in Primary Care Patients: Results of a Pilot Study in a Pre-Post Design. Kesztyüs, D., Cermak, P., Gulich, M., et al.[2022]

In the CALERIE study, calorie restriction (CR) led to significant weight loss, explaining 41% of the variance in weight loss among participants, but the timing of meals also played a crucial role.

Shorter eating intervals and consistent timing for the first and last meals were associated with greater weight loss and enhanced adherence to CR, suggesting that optimizing meal timing could improve the effectiveness of CR protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations between the timing of eating and weight-loss in calorically restricted healthy adults: Findings from the CALERIE study. Fleischer, JG., Das, SK., Bhapkar, M., et al.[2022]

In a 12-week study involving 23 obese adults, time-restricted feeding (TRF) with an 8-hour eating window was found to be safe, as there were no significant changes in self-reported adverse events or disordered eating patterns.

The study suggests that TRF can effectively support weight loss in obese individuals without negatively impacting their health or body image perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of 8-h time restricted feeding in adults with obesity. Gabel, K., Hoddy, KK., Varady, KA.[2019]

Citations

1. ijbnpa.biomedcentral.com ijbnpa.biomedcentral.com/articles/10.1186/s12966-024-01657-9

Comparing caloric restriction regimens for effective weight ... Randomized controlled trials have confirmed the effectiveness of four prevalent caloric restriction regimens in reducing obesity-related health ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3014770/

Caloric Restriction in Humans: Impact on Physiological ... This study of nature of caloric restriction resulted in ∼15% weight loss (B), in changes in energy expenditure and physical activity (C), and many ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03411356

NCT03411356 | Intermittent Fasting Versus Daily Caloric ... Short-term studies suggest IMF produces 3-8% weight loss in individuals with overweight and obesity. However, few studies have compared IMF to DCR and no ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2114833

Calorie Restriction with or without Time-Restricted Eating ... In this 12-month trial, we found that the 8-hour time-restricted–eating regimen did not produce greater weight loss than the regimen of daily ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1658361225000186

Evaluation of the effectiveness of intermittent fasting versus ... Pooled analysis revealed that IF led to a more significant decrease in BMI than ER (−0.44 [-0.88 to −0.01]; p < 0.01). Additionally, IF resulted in a slightly ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35443107/

Calorie Restriction with or without Time-Restricted Eating ... Conclusions: Among patients with obesity, a regimen of time-restricted eating was not more beneficial with regard to reduction in body weight, ...

7. nature.com nature.com/articles/s41586-024-08026-3

Dietary restriction impacts health and lifespan of ... The 40% CR mice showed rapid body weight decline at the onset of DR and lost an average of 24.3% of their 6-month-old body weight by 18 months ...