Effect of Intensive Nutrition Training, Education, and Support in Gestational Diabetes - The INTENSE-GDM TRIAL

Study Overview
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Brief Summary
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The treatment of gestational diabetes (GDM) primarily revolves around consuming an optimal diet that does not cause blood glucose levels to become excessively high and provides an adequate supply of micro- and macronutrients without resulting in excessive weight gain during pregnancy. In some cases, it may become necessary to supplement with insulin during pregnancy. However, insulin treatment is associated with personal, health-related, and healthcare cost-related implications. The rationale for this study is the lack of knowledge regarding whether the extent of support and guidance from a dietitian during pregnancy has an impact on the treatment outcomes for both the mother and the child in cases of GDM. The overall objective is to investigate differences in clinical, cost-related, and patient-reported outcomes between women with GDM randomised to either intensive dietary therapy or standard dietary care (control). The primary endpoint is the effect of intensive dietary therapy on the likelihood of remaining treated with diet only vs. needing insulin therapy. The study design is a randomised controlled parallel group open-label effectiveness trial including 232 women with GDM.

Detailed Description
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Gestational diabetes (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. The disease is characterized by hyperglycaemia and a marked insulin resistance secondary to placental hormonal release. Risk factors for developing GDM in pregnancy include obesity, excessive gestational weight gain, previous GDM, glucosuria, family history of diabetes, ethnicity, and hypertension. Hyperglycaemia is associated with serious short- and long-term complications for mother and child including delivering large-for-gestational-age (LGA) babies, macrosomia, preterm birth, caesarean section, preeclampsia, birth injury, respiratory distress syndrome, neonatal hypoglycaemia, jaundice, and increased admission to neonatal intensive care unit (NICU). First-line treatment in GDM after diagnosis is dietary therapy including a systematic and detailed dietary assessment to identify relevant areas for adjusting the diet and overall lifestyle. The overall goals with dietary therapy are 1) To provide adequate calories and micro- and macronutrients to meet the needs of pregnancy consistent with maintaining normoglycaemia, 1) To improve glycaemic control; and 3) To secure appropriate gestational weight gain and avoid excessive weekly gestational weight gain. Currently, no evidence exists for specific recommendations concerning the optimal frequency, intensity, or duration of visits with a dietitian for improving maternal, foetal, or neonatal outcomes. National clinical guidelines for treatment of GDM recommends up to three visits with a dietitian depending on the time of diagnosis. However, in the latest national clinical guidelines under review this has been changed to only one visit. In most cases dietary improvements are sufficient to achieve glycaemic goals but around one third of all women with GDM will need insulin therapy at some point during pregnancy. Decision about additional insulin therapy is based on a combination of ultrasound findings and dietary glycemic control as indicated by the blood glucose protocol as assessed by an obstetrician. Insulin therapy can improve glycaemic control and has been shown to be effective in reducing the rate of macrosomia in GDM. But use of insulin during pregnancy is also associated with several clinical implications, increased hospital and medical costs as well as higher costs in relation to delivery, and neonatal care, and personal burden affecting women with GDM. In summary, the most optimal way to deliver dietary therapy to women with GDM is not known. The possibility that intensive dietary therapy may reduce the need for initiating insulin treatment without increasing hospital service costs for these women in comparison with women receiving standard dietary care needs to be explored. The overall objective is to investigate the effectiveness and hospital service costs of implementing an intervention with intensive dietary counselling and support during pregnancy in women with GDM. The INTENSE-GDM trial is a randomised controlled parallel group open-label effectiveness trial including 232 women with GDM. Participants will attend one consultation with a dietitian in the standard care group and up to 5 consultations (including 2 mandatory follow-up visits and 2 optional follow-up visits) with a dietitian in the intensive dietary counselling group. Both groups will receive one end-of-intervention telephone call. The primary endpoint is the percentage of women with GDM treated with insulin therapy in the intervention group and the control group at delivery. Secondary endpoints include maternal endpoints (changes in body weight from referral to delivery, changes in glycaeted hemoglobin A1c from referral to delivery, time to insulin treatment onset, mean prescribed initial and maximal insulin dose, neonatal endpoints (percentage of LGA, small for gestational age, macrosomia new-borns respectively, percentage of new-borns with neonatal hypoglycaemia and percentage of new-borns admitted to NICU). Descriptive/exploratory endpoints include changes in maternal endpoints (percentage of cases of preeclampsia, preterm births, cases of acute and planned caesarean sections), neonatal endpoints (percentage of cases of neonatal jaundice, questionnaires (diabetes diet-related quality of life, well-being, perceived autonomy support and competence in diet and diabetes, treatment satisfaction and physical activity during pregnancy). Hospital costs will be analysed for the two study groups (intensive dietary therapy vs. standard care) including costs from referral with GDM to discharge after delivery divided into the categories 1) outpatient contacts and costs related to the treatment of GDM, 2) delivery costs, 3) inpatient costs after delivery for mother and offspring separately, including NICU costs and 4) total net costs. Additionally, adherence to intervention (number of no shows for planned visits), number and types of visits (face-to-face, video and telephone), changes in dietary intake and adverse events will be recorded.

Official Title
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Effect of Intensive Nutrition Training, Education, and Support Versus Standard Care in Reducing the Need for Insulin Therapy in Gestational Diabetes (INTENSE-GDM): A Randomised Controlled Trial

Conditions
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GDM, Gestational Diabetes, Nutritional and Metabolic Diseases, Nutrition Therapy, Medical Nutrition Therapy

Intervention / Treatment
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* Behavioral: Dietary treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed women with GDM referred to Department of Obstetrics Herlev Hospital Women diagnosed with GDM based on 2-hour OGTT plasma glucose value ≥ 9.0 mmol/l Women diagnosed with GDM based on at least 2 plasma glucose measurements above targets (either pre-prandial ≥6.0 mmol/l, or 2-hours postprandial ≥8.0 mmol/l) GA at GDM diagnosis ≤ 34 Provided voluntary written informed parental consent in Danish or English or after translation by an interpreter for non-Danish and non-English speaking parents Exclusion Criteria: Pre-pregnancy BMI ≤25 kg/m2 Bariatric surgery Other intercurrent illness (e.g., cancer, ulcerative colitis) as judged by medical experts Uncontrolled medical issues, as judged by medical experts Concomitant participation in other clinical trials that could interfere with the INTENSE- GDM Trial as evaluated by the principle investigator Unable to understand the informed consent/procedures regardless of spoked language
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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The INTENSE-GDM trial is a randomised controlled parallel group open-label effectiveness trial. Participants will be randomised to either an intensive dietary counselling group or a usual dietary care group (control group) in a 1:1 ratio.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive dietary care group<br>Women randomised to the intensive dietary intervention group will receive one initial dietary counselling consultation (60 min), and two mandatory follow-up consultations (2 x 30 min) with a dietitian. In addition, participants in this group will be offered 1-2 follow-up consultations (1-2 x 15-30 min) if needed. | Behavioral: Dietary treatment<br>* Dietary counselling<br>|
| Active Comparator: Standard dietary care group<br>Women randomised to the standard dietary care group will receive one dietary counselling consultation (60 min) according to the initial dietary counselling described without any follow-up consultations with a dietitian. Participants are encouraged to follow their dietary plan until delivery. | Behavioral: Dietary treatment<br>* Dietary counselling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of insulin-treated | Percentage of women with GDM treated with insulin therapy in the two study groups | From date of randomisation until date of child delivery, assessed from study completion up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal body weight | Changes in body weight, kg | From date of randomisation until date of child delivery, assessed from study completion up to 24 weeks | 
| Maternal glycaemic control | Changes in maternal HbA1c, mmol/mol | From date of randomisation until date of child delivery, assessed from study completion up to 24 weeks | 
| Onset of insulin treatment | Time to insulin treatment onset, days | From date of randomisation until date of first insulin prescription, assessed from study completion up to 24 weeks | 
| Prescribed insulin | Mean prescribed initial and maximal insulin dose, units/kg body weight | From date of randomisation until date of child delivery, assessed from study completion up to 24 weeks | 
| Large for gestational age (LGA) | LGA new-borns, % | At delivery, assessed from study completion up to 24 weeks | 
| Small for gestational age (SGA) | SGA new-borns, % | From date of randomisation until date of child delivery, assessed from study completion up to 24 weeks | 
| Macrosomia (birth weight >4,500 g) | Newborns with macrosomia, % | From date of randomisation until date of child delivery, assessed from study completion up to 24 weeks | 
| Neonatal hypoglycaemia | New-borns with neonatal hypoglycaemia, % | From date of randomisation until data of discharge after child delivery, assessed from study completion up to 24 weeks | 
| Admission to neonatal intensive care unit (NICU) | New-borns admitted to NICU, % | From date of randomisation until data of discharge after child delivery, assessed from study completion up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GDM, Nutrition care, Dietary management, Insulin use, Hospital costs