Very-Low Energy Diet for Preconception Health

Overseen By Shannon Considine, MPH, MSW

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Michigan

Must not be taking: Anti-obesity drugs

Disqualifiers: Heart, kidney, liver, autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

352 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have recently used anti-obesity drugs or appetite suppressants.

What data supports the effectiveness of the treatment Very-low energy Diet (VLED) for preconception health?

Very-low energy diets (VLEDs) have been shown to achieve greater long-term weight loss compared to behavioral programs alone, with studies indicating a weight loss of 1.5-2.5 kg per week. They are effective in reducing liver size and abdominal fat, which can be beneficial before obesity surgery, and may improve glucose metabolism in type 2 diabetes better than conventional diets. ^{1 2 3 4 5}

Is a very-low energy diet (VLED) generally safe for humans?

Very-low energy diets (VLEDs) can lead to rapid weight loss, which may raise concerns about maternal nutrition and potential risks to early fetal development, such as exposure to ketosis. However, they have been used successfully in managing obesity, diabetes, and hypertension, suggesting they can be safe when monitored properly. ^{6 7 8 9 10}

How does the Very-low energy Diet (VLED) treatment differ from other treatments for preconception health in women with obesity?

The Very-low energy Diet (VLED) is unique because it offers substantial and rapid weight loss before pregnancy, which is crucial for improving pregnancy outcomes in women with obesity. Unlike lifestyle modifications that result in modest weight loss or bariatric surgery that may pose risks to the offspring, VLED provides a balanced approach by achieving significant weight loss without surgical intervention. ^{6 7 10 11 12}

What is the purpose of this trial?

Our hypothesis is that aggressive preconception weight loss in obese women will improve the metabolic health of the mother and the intrauterine environment. An optimized developmental environment will normalize fetal growth and improve clinical fetal and infant outcomes, and theoretically reduce future susceptibility to obesity and cardiometabolic disease.

Research Team

Amy Rothberg, MD, PhD

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for obese women with a BMI between 30 and 45 who want to lose weight before getting pregnant. They should not have infertility issues, significant medical conditions, or a history of certain treatments like bariatric surgery. Healthy-weight women with a BMI up to 25 can also join.

Inclusion Criteria

BMI > 30 ≤ 45 for obese participants

BMI ≤ 25 for healthy body weight participants

No known risk factors for tubal disease

Exclusion Criteria

My endometriosis is classified as severe.

Current pregnancy

Conditions that would complicate pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preconception Weight Loss Intervention

Participants undergo a dietary intervention aimed at preconception weight loss, with a focus on either a very-low energy diet (VLED) or standard of care (SOC) nutrition counseling.

16 weeks

Pregnancy Monitoring

Participants are monitored throughout pregnancy with assessments of fetal growth, maternal metabolite levels, and other health indicators.

Each trimester of pregnancy (between 8-12 weeks, between 18-22 weeks, and between 28-34 weeks)

Delivery and Immediate Postpartum

Assessment of delivery outcomes, including mode of delivery and immediate neonatal health metrics such as body fat mass and metabolome analysis.

At delivery

Infant Follow-up

Infant growth and health are monitored at regular intervals to assess long-term outcomes related to the preconception intervention.

Delivery to 12 month follow-up

Treatment Details

Interventions

• Very-low energy Diet (VLED)

Trial Overview The study tests if losing weight through a Very-low energy Diet (VLED) before conception leads to better health for the mother and baby compared to standard care. It aims to see if this improves birth outcomes and reduces future obesity risks in children.

Participant Groups

Group I: Obese - Very low energy diet (VLED) Experimental Treatment 1 Intervention

Participants will adopt a very-low energy diet

Group II: Obese - Standard of care (SOC) Experimental Treatment 1 Intervention

Participants will receive the standard of care for obese women looking to become pregnant.

Group III: Lean - Standard of care (SOC) Experimental Treatment 1 Intervention

Participants will receive the standard of care for lean women looking to become pregnant.

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Very-low-energy diets (VLEDs) combined with behavioral programs resulted in a significant weight loss of -3.9 kg at 12 months compared to behavioral programs alone, indicating their efficacy in long-term weight management.

The study found that VLEDs were generally well-tolerated, with a similar rate of treatment discontinuation compared to control groups and only one serious adverse event reported, suggesting they could be safely used more widely than current guidelines recommend.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of very-low-energy diets in the management of weight loss: a systematic review and meta-analysis of randomized controlled trials. Parretti, HM., Jebb, SA., Johns, DJ., et al.[2022]

This study is testing a lifestyle intervention called 'Healthy for my Baby' aimed at improving diet and lifestyle in 68 non-infertile overweight or obese women and their partners during the preconception period, using motivational interviews and a mobile app for self-monitoring.

The primary goal is to enhance women's diet quality, measured by the C-HEI 2007 score, with the potential to reduce pregnancy complications and prevent future health issues, indicating a need for larger trials if successful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Healthy for My Baby Research Protocol- a Randomized Controlled Trial Assessing a Preconception Intervention to Improve the Lifestyle of Overweight Women and Their Partners. Hardy, I., Lloyd, A., Morisset, AS., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Clinical effectiveness of very-low-energy diets in the management of weight loss: a systematic review and meta-analysis of randomized controlled trials. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Preoperative weight loss with a very-low-energy diet: quantitation of changes in liver and abdominal fat by serial imaging. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Comparison of a low-energy diet and a very low-energy diet in sedentary obese individuals: a pragmatic randomized controlled trial. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Very low energy diets in the treatment of obesity. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Postmenopausal women's experiences of weight maintenance following a very low energy diet. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Time to pregnancy after a prepregnancy very-low-energy diet program in women with obesity: substudy of a randomized controlled trial. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Using a Very Low Energy Diet to Achieve Substantial Preconception Weight Loss in Women with Obesity: A Review of the Safety and Efficacy. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Dieting behaviors and risk of neural tube defects. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Management of gestational weight gain in obese or overweight women based on resting energy expenditure: A pilot cohort study. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

A case of obesity, diabetes and hypertension treated with very low calorie diet (VLCD) followed by successful pregnancy with intrauterine insemination (IUI). [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Healthy for My Baby Research Protocol- a Randomized Controlled Trial Assessing a Preconception Intervention to Improve the Lifestyle of Overweight Women and Their Partners. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

Diet and Lifestyle Before and During Pregnancy - Practical Recommendations of the Germany-wide Healthy Start - Young Family Network. [2020]