NDPP-NextGen: A Clinical Trial to Reduce Intergenerational Obesity and Diabetes Risks

Study Overview
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Brief Summary
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The goal of this clinical trial is to test an enhanced version of the National Diabetes Prevention Program (NDPP-NextGen) that is tailored to young women in childbearing years. The investigators will recruit 360 women aged 18-39 years with overweight/obesity who are not currently pregnant, but likely to conceive within 24 months. Women will be randomized to NDPP-NextGen or a usual care control group. The NDPP-NextGen group will participate in the adapted NDPP online group class across 12 months, and the control group will get a packet of information about how to be healthy before, during and after pregnancy. The main goals of the study are: to assess effects of NDPP-NextGen on pre-pregnancy blood sugar and early pregnancy BMI to assess effects of NDPP-NextGen on weight gain and behavioral outcomes during pregnancy to explore effects of NDPP-NextGen on infant's percentage of fat tissue at birth All participants will complete up to 4 research visits: baseline, conception, mid-pregnancy, and delivery. These visits will include: Questionnaires about health, diet, activity, smoking, self-confidence, and depression Body size measurements Fasted blood draws Participants will also be asked to weigh themselves weekly using home scales that are connected to the research database. At the delivery visit, investigators will measure the baby's body size and collect a cord blood sample.

Detailed Description
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Intrauterine exposure to maternal overweight/obesity and diabetes transmits risks to offspring, triggering a disease cycle across generations. Over half of US women have overweight or obesity at conception and  10% of pregnancies are affected by diabetes, exposing nearly 2 million infants each year. Prenatal lifestyle interventions are well-studied, yet begin too late to impact the critical period of conception and early pregnancy. Starting interventions before conception may be key to halting the disease cycle. However, prior research is limited, often lacks offspring outcomes (especially sensitive measures), includes mostly white and affluent participants, and has been challenged to identify women likely to conceive soon. Further research is needed on scalable strategies to improve maternal-child health during preconception and early pregnancy, especially for racial and ethnic minority or low-income women with disparately high prevalence of obesity and diabetes. The National Diabetes Prevention Program (NDPP) is a widely-disseminated lifestyle intervention to reduce weight and glycemia that has untapped potential to improve maternal-child health. From an implementation science perspective, the NDPP has greater potential impact than new interventions that are unlikely to be scaled up, even if efficacious. Denver Health has delivered the NDPP to >1600 adults since 2013, including >350 young women. Preliminary data shows that the NDPP may reduce peri-conceptional risks in diverse, low-income women. While limited engagement by younger women in the NDPP is a concern, strategies to increase engagement (motivational pre-sessions, remote delivery, and classes specially for young women) are promising. For example, young women attended the 12-month NDPP for 64 days longer after receiving a pre-session, with 2.0 kg/m2 lower preconception BMI and 0.4% lower A1c in early pregnancy, than controls. To plan a preconception trial, the investigators developed a 2-step screening protocol to 1) use electronic health record data (e.g., contraceptive use) to identify women who are more likely to conceive by 24 months (36% vs. 13% for all young women), and 2) outreach to confirm current family planning to expect ≥60% conception, based on preliminary data showing that 73% conceived by 24 months if they endorsed intention to conceive or being sexual active without highly effective contraception. The investigators propose a randomized controlled trial of an enhanced NDPP (NDPP-NextGen) initiated before pregnancy to evaluate effects on maternal-child health. They will recruit 360 women aged 18-39 years with overweight/obesity who are likely to conceive within 24 months. Women will be randomized to NDPP- NextGen or a usual care control group. The specific aims are 1) to assess effects of NDPP-NextGen on peri- conceptional BMI and prenatal glycemia; 2) to assess effects of NDPP-NextGen on gestational weight gain and behavioral outcomes in pregnancy; and 3) to explore effects of NDPP-NextGen on neonatal adiposity and explanatory mechanisms.

Official Title
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NDPP-NextGen: A Clinical Trial to Reduce Intergenerational Obesity and Diabetes Risks

Conditions
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Overweight or Obesity

Intervention / Treatment
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* Behavioral: NDPP-NextGen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established patient at Denver Health Biologically female (inclusive of all gender identities) Aged 18-39 years English- or Spanish-speaking BMI ≥25 kg/m2 (≥23 kg/m2 if Asian race) Activities that lead to pregnancy in past 3 months Interested in pregnancy within 24 months, including: High interest (actively trying to conceive) General interest (not actively trying but wanting to become pregnant in the foreseeable future) Neutral interest (not planning pregnancy or using contraception for religious reasons) Exclusion Criteria: Currently pregnant Non-gestational diabetes (type 1, type 2) Long-acting contraceptives (intrauterine device, implant, injection) with plans to continue for >1 year (barrier & short-acting hormonal contraception permitted given ease of discontinuing to facilitate pregnancy) Medical procedures (e.g., tubal ligation, hysterectomy) or conditions that impede pregnancy (e.g., polycystic ovarian syndrome) Documented infertility or unsuccessfully trying to conceive for ≥12 months Prior participation in the NDPP

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1 to a 12-month lifestyle intervention promoting healthy diet and activity to reduce body weight (NDPP-NextGen), or usual care
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Lifestyle<br>Women in the Healthy Lifestyle group will be invited to attend the online NDPP-NextGen class which will cover how to eat healthy, be active, and lose weight before getting pregnant. The classes will be led by a trained Lifestyle Coach. Each class lasts about 1 hour. Classes initially meet about once a week (for the first 6 months), then twice a month (for the next 3 months), and then once a month (for the last 3 months). Classes will meet virtually through video-conference. Lifestyle coaches will also call participants in between classes to discuss how participants are doing, answer questions, and provide reminders for upcoming classes. Prior to the first class, women will also participate in a pre-session designed to increase NDPP engagement via discussion of diabetes risks and treatment options (i.e., clarify relevance) and motivational interviewing to resolve barriers. | Behavioral: NDPP-NextGen<br>* NDPP-NextGen will incorporate content on preconception/prenatal health into standard NDPP. Participants will be encouraged to make sustainable improvements in diet and activity, but without pre-set goals to better accommodate diverse, low-income populations. Upon pregnancy, recommendations will adjust to support appropriate GWG, breastfeeding, and postpartum weight loss. We will provide education on diet and activity during pregnancy/postpartum, including sufficient energy intake and exercise safety to support the growing fetus. NDPP-NextGen will include 3 strategies to better engage young women. (1) Pre-sessions to increase knowledge of diabetes risks, self-efficacy, and readiness to change using motivational interviewing techniques. (2) Delivering classes remotely (via phone- and video-conference) to facilitate participation regardless of inclement weather, dependent care, illness, transportation, etc. (3) Offering classes specially for young women to increase personal relevance.<br>|
| No Intervention: Healthy Women<br>Women in the Healthy Women group get a packet of information standardly given in OB clinics about how to be healthy before, during and after pregnancy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI in early pregnancy | Height and weight will be measured and combined to report BMI at the post-conception research visit occurring at 6-8 weeks gestation. | 6-8 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemia in early pregnancy | Fasting glucose | 6-8 weeks gestation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Body mass index, Pre-conception, Diabetes Mellitus, Diet, Gestational diabetes, Neonatal adiposity, Maternal and Child Health, Overweight, Obese, Pregnancy, Randomized Control Trial, Weight, adverse maternal outcomes, Diabetes Prevention Program, glucose, gestational weight gain, lifestyle intervention, usual care, remote delivery, young women