Clinical trial NCT06355154: Effects of Moderate Carbohydrate Consumption on Metabolic and Obstetric Outcomes in Pregnant Women With Insulin-treated Diabetes- A Randomized Controlled Trial
Official title: Effects of Moderate Carbohydrate Consumption on Metabolic and Obstetric Outcomes in Pregnant Women With Insulin-treated Diabetes- A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes in Pregnancy
Keywords: Diabetes in pregnancy
Glycemic balance
Low Carbohydrates
Time in range
Ketosis
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label, randomized controlled trial
Primary purpose: TREATMENT

Brief summary: Diabetes during pregnancy increases maternal and fetal complications, necessitating optimal glycemic control. The standard care diet (SCD, ≥175g/day carbohydrate) lacks robust evidence, particularly for pregnancies requiring intensive insulin treatment (IIT). This RCT investigates whether a moderate carbohydrate diet (MCD, ≤120g/day) versus SCD improves glycemic control and alters metabolomic profiles in pregnant individuals on IIT.

Aims: To compare the efficacy and safety of a SCD versus MCD on glycemic control, metabolomic signatures, and pregnancy outcomes in pregnant individuals on IIT.

Detailed description: Effects of moderate carbohydrate consumption on metabolic and obstetric outcomes in pregnant women with insulin-treated diabetes- A randomized controlled trial

1. Scientific Background:

   1.1 Diabetes Mellitus in Pregnancy: Diabetes during pregnancy (pre-gestational type 1 or 2, or gestational diabetes) is associated with complications for both the mother (polyhydramnios, miscarriage, hypertension, preeclampsia, need for instrumental delivery) and the fetus/neonate (birth defects, macrosomia, shoulder dystocia, respiratory distress, hyperbilirubinemia, hypoglycemia). (1),(2) ,(3),(4). The incidence of all forms of diabetes during reproductive age is increasing(5).

   1.2 Dietary carbohydrate consumption during pregnancy: Current guidelines recommend a minimum carbohydrate consumption of 175g/day for all pregnant women, regardless of diabetes status. This is based on a theoretical calculations rather than clinical evidence (6). Some concerns with carbohydrate restriction during pregnancy include disrupting the maternal-fetal glucose gradient, increased fetal ketone exposure, micronutrient deficiency, and increased maternal triglycerides/free fatty acids(7).

   However, recent studies found no correlation between moderate carbohydrate restriction (\<175g/day but \>120g/day) and increased ketosis(8),(9),(10). Reducing carbohydrates may help reduce postprandial hyperglycemia in patients on intensive insulin therapy(11),(12).These findings call into question the hypothetical assumption that a minimum of 175 gr of CHO is required during pregnancy.
2. Research Objective:

   The primary objectives of the trial are to determine:
   * To assess the effectiveness and safety of moderate carbohydrate consumption restriction (MCD) in enhancing glycemic control.
   * To investigate the impact of MCD on the metabolomic profile of pregnant individuals with diabetes requiring intensive insulin treatment (MDI/CII).
3. Expected Significance:

The importance of this study lies in:

1. Challenging the commonly accepted but theoretical recommendation of 175g/day minimum carbohydrate intake during pregnancy.
2. Evaluating if moderate carbohydrate restriction can improve glycemic control and pregnancy outcomes in women with diabetes requiring intensive insulin therapy, without major adverse effects.

4.Detailed Description of the Proposed Research: 4.1 Study Design: This is an open label, randomized controlled trial comprising 120 pregnant individuals (18-45 years) with any form of diabetes requiring intensive insulin therapy. Pregnant individuals on IIT will be randomized to standard carbohydrate diet (\>175g/day) or moderate carbohydrate diet (120g/day) group.

Key Measurements/Data Collection:

* Continuous glucose monitoring (CGM) to assess time in range (TIR) and other glycemic parameters.
* Anthropometrics (weight, height, BMI).
* Dietary intake data (FFQs, 24-hr recalls, 3-day food diaries).
* Blood tests (HbA1c, glucose, c-peptide, lipids, etc).
* Fetal growth monitoring via ultrasound.
* Cord blood c-peptide at delivery.
* Neonatal and maternal post-delivery outcomes (mode of delivery, weight, complications, etc).
* Maternal metabolomics (fasting blood sample). 4.3 Study Visits:
* Screening/baseline visit to assess eligibility.
* Dietary counseling and medical team visits every 2 weeks until 32 weeks, then weekly or as be decided by the medical team according to patients needs.
* Fetal ultrasounds start at 28 weeks, twice monthly or more.
* Final visit at 35-38 weeks for metabolomics sample. 4.4 Safety Monitoring:
* No intended calorie restriction.
* CGM to adjust insulin and avoid hypoglycemia.
* Home ketone monitoring.
* Ultrasound fetal growth monitoring. 4.5 Metabolomics Analysis:
* LC-MS analysis to detect \>400 metabolites.
* Assess effects on micronutrients, carbs, lipids, ketones, amino acids.
* Identify metabolic pathways affected and correlate with pregnancy outcomes. 4.6 Research Calculation: 120 participants total (60 per group). 80% power to detect 7% difference in time in range (TIR) between group. Assumptions based on literature, including CONCEPTT study standard deviation 4.7 Ethical Approval: Study will follow Declaration of Helsinki. Institutional ethics approval obtained 5. Research Environment: The study will be conducted at 3-4 major medical centers in Israel with expertise in high-risk pregnancies. Qualified clinical staff including doctors, nurses, dietitians and researchers will be involved in participant recruitment, intervention delivery, data collection and analysis. Necessary equipment like CGMs, metabolomics instruments, etc. are available at these sites.

Eligibility criteria: Inclusion Criteria:

* • Pregnant women with singleton pregnancies.

  * Over 18 years old.
  * Diagnosis of GDM- 3-h 100-g OGTT according to the American College of Obstetricians and Gynecologists supported by the American Diabetes Association, Or Diagnosis of type 1 or 2 diabetes before pregnancy, Or Diagnosis of early GDM by either OGTT in the first trimester or elevated blood glucose measurements in the fasting (above 95mg/dl) or the postprandial (above 140 mg/dl) state.
  * Are already on or intended to start intensive insulin treatment (at leased 2 injections of insulin per day) or wear an insulin pump.
  * Are willing to wear a continuous glucose monitoring system.
  * BMI of 18.5-42 kg/m2 at the time of diagnosis.

Exclusion Criteria:

* Individual with risk factors for:

  * Placental insufficiency.
  * Hypertension.
  * Renal disease.
  * Thrombophilia
  * Rheumatologic disease.
  * A history of preeclampsia, or fetal growth restriction (IUGR).
  * Individuals with a history of preterm labor, or concomitant therapy with β-blockers or glucocorticoids.
  * Individuals who smoke and/or consume any amount of alcohol during pregnancy.

Primary outcomes:
measure: Time in range
timeFrame: 24 hours
measure: Time above range
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Hospital
Study officials:
References:
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