Clinical trial NCT05843175: Maternal ExeRcIse Timing to Optimise Postprandial Glucose in Type 1 Diabetes
Official title: Maternal ExeRcIse Timing to Optimise Postprandial Glucose in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pregnancy in Diabetic
Type 1 Diabetes
Lead sponsor: University of Graz
Sponsor class: OTHER
Collaborators: name: Medical University of Graz
First posted: 2023-05-06
Enrollment: 20
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomised, single-centre, controlled crossover in parallel groups (pregnant and non-pregnant women with type 1 diabetes)
Primary purpose: SUPPORTIVE_CARE

Brief summary: Poor glycaemic control in pregnancy is a major factor leading to obstetric complications and future maternal-offspring diseases. This phenomenon is evidenced in women with type 1 diabetes (T1DM), and is worrisome since it is aggravating the disease burden of this and next generations.

Exercise is a promising tool to improve glucose control during pregnancy and thus avoid adverse consequences.

The MERIT1D study will explore when is exercise (before or after lunch) more effective to improve postprandial glycaemic control in pregnant and non-pregnant women (of reproductive age) with T1DM, and the mechanisms underlying these metabolic responses.

Detailed description: Poor glycaemic control in pregnancy is a major factor leading to obstetric complications and future maternal-offspring diseases (e.g., macrosomia, diabetes). This phenomenon is evidenced in women with type 1 diabetes (T1DM), and is worrisome since it is aggravating the disease burden of this and next generations. Therefore, to find strategies aimed at breaking this intergenerational cycle has become a high-priority. Exercise is a promising tool to improve short-term glycaemic responses such as postprandial glucose peaks and glucose variability, and thus reduce adverse maternal-neonatal outcomes. However, it is unknown which timing of exercise is more effective to optimise postprandial glycaemic control in pregnant women with T1DM, and non-pregnant women (of reproductive age) with T1DM. The mechanisms underlying these benefits in T1DM and pregnancy are also to be established.

The MERIT1D project will unravel which timing of exercise (before or after a meal at lunchtime) is more effective to optimise postprandial glycaemic control in pregnant and non-pregnant women with T1DM, and the mechanisms underlying these metabolic responses. Ten pregnant women with T1DM and ten non-pregnant women with T1DM will be involved in this randomised controlled crossover trial.

Pregnant women at gestational week 16 and 35 (experimental phases 1 and 2, respectively), and non-pregnant peers once after recruitment (experimental phase 1), will undergo 3 experimental conditions within 10 days (random order): pre-meal exercise, post-meal exercise, and non-exercise meal.

Each experimental phase will entail participants attending 4 times to the research centre. Therefore, pregnant women will come to the research centre for a total of 8 study visits, while non-pregnant women will come only to 4 study visits. The acute exercise stimulus will consist of a well-controlled submaximal walking test. The standardised meal provided will consist of a mixed milkshake equivalent to the 35 % of their resting energy expenditure, being made up of approximately 45% carbohydrates, 35% fat, and 20% proteins. Postprandial glycaemic responses will be continuously monitored using last-generation glucose monitoring systems during the 10-day period. Immunometabolic markers (e.g., lipids, cytokines) will be determined in maternal blood and placenta samples.

The MERIT1D study will contribute to the understanding of exercise timing in T1DM and pregnancy, and its underlying mechanisms. This will translate into a better clinical prediction, diagnosis, prognosis and treatment of glycaemic dysregulations, and into more effective exercise programmes for pregnant and non-pregnant women with T1DM.

Eligibility criteria: Inclusion Criteria:

* Pregnant women and non-pregnant women with T1DM aged 20-40 years
* Having a BMI of 18-29.9 kg/m2 at pre-pregnancy (pregnant women) or recruitment (non-pregnant)
* Clinical diagnosis of T1DM, or/and multiple daily insulin injections for \>1 year, and/or using insulin pump therapy (open-loop).
* Willingness to provide informed consent to participate in the MERIT1D study.
* Being able to read and speak German, English or Spanish well enough to completely understand the instructions, provide informed consent and conduct the experimental procedures.

Exclusion Criteria:

* Having poor glycaemic control HbA1c\>10% (86 mmol/mol).
* Recurrent severe hypoglycaemia; hospitalisation for diabetic ketoacidosis during the last year.
* Women who smoke or drink alcohol frequently, or require complex diets.
* Having polycystic ovarian syndrome, poorly controlled asthma/allergy, uncontrolled thyroid diseases or hypertension, diabetic ketoacidosis, hepatitis B, hepatitis C, HIV.
* Having severe autoimmune/immunodeficiency, macrovascular, renal, or neuromuscular disease, or severe retinopathy or neuropathy.
* Having any other cardiovascular, pulmonary, orthopaedic, neurologic, psychiatric, or terminal disease, or any other acute/chronic disorder that, in the opinion of the local clinician/researcher, would preclude participation and successful completion of the protocol, or that would directly influence the study results.
* Use of any medication (e.g., steroids), that, in the opinion of local clinician/researcher, would negatively impact or mitigate full participation and completion, or could influence the study results.
* Any condition that would interfere with compliance or the results, as judged by the Investigator
* Pregnant women: having multiple pregnancy
* Pregnant women: evidence of incompetent cervix, ruptured membranes, placenta previa, foetal malformation, or foetal death.

Primary outcomes:
measure: Percentage of time spent in the euglycemic range for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
measure: Percentage of time spent in the euglycemic range for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary outcomes:
measure: Percentage of time spent in hypoglycemia for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
measure: Percentage of time spent in hypoglycemia for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
measure: Percentage of time spent in hyperglycemia for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
measure: Percentage of time spent in hyperglycemia for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
measure: Differences in postprandial glucose levels 1-, 2-, and 4-hours post-experiment
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 4 h/day)
measure: Differences in postprandial glucose levels 1-, 2-, and 4-hours post-experiment
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 4 h/day)
measure: Number of hypoglycaemic events for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
measure: Number of hypoglycaemic events for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
measure: Number of hyperglycaemic events for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
measure: Number of hyperglycaemic events for the 24 hours after each experimental condition
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
measure: Percentage of time spent in nocturnal euglycemia within each experimental day
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 00:00 am - 05:59 am)
measure: Percentage of time spent in nocturnal euglycemia within each experimental day
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 00:00 am - 05:59 am )
measure: Percentage of time spent in diurnal euglycemia within each experimental day
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 6.00 am - 23:59 am)
measure: Percentage of time spent in diurnal euglycemia within each experimental day
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 6.00 am - 23:59 am)
measure: Area under the curve of glycaemic exposure
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 8 hours/day)
measure: Area under the curve of glycaemic exposure
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 8 h/day)
measure: Glycaemic variability (standard deviation)
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
measure: Glycaemic variability (standard deviation)
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
measure: Glycaemic variability (coefficient of variation)
timeFrame: assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
measure: Glycaemic variability (coefficient of variation)
timeFrame: assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
measure: Maternal glucose metabolism
timeFrame: assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
measure: Maternal glucose metabolism
timeFrame: assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
measure: Maternal lipid profile
timeFrame: assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
measure: Maternal lipid profile
timeFrame: assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
measure: Maternal inflammatory markers
timeFrame: assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
measure: Maternal inflammatory markers
timeFrame: assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
measure: Placenta weight
timeFrame: assessed at birth - 30 minutes
measure: Placenta biopsies
timeFrame: collected at birth - 1 hour
measure: Neonate weight
timeFrame: assessed at birth - 5 minutes
measure: Placenta efficiency
timeFrame: estimated after birth - 3 minutes
Other outcomes:
measure: Placenta completeness
timeFrame: assessed at birth - 20 minutes
measure: Neonate height
timeFrame: assessed at birth - 5 minutes
measure: Neonate ponderal index
timeFrame: estimated after birth - 3 minutes
measure: Neonate anthropometrics
timeFrame: assessed at birth - 10 minutes
measure: Neonate Apgar score
timeFrame: assessed at birth - 5 minutes
measure: Small for gestational age
timeFrame: assessed after birth - 5 minutes
measure: Large for gestational age
timeFrame: assessed after birth - 5 minutes
measure: Physical fitness (muscle strenght)
timeFrame: assessed in the phase 1, at visit nº 1 (10 minutes)
measure: Physical fitness (muscle strenght)
timeFrame: assessed in the phase 2 (only pregnant women), at visit nº 5 (10 minutes)
measure: Physical fitness (flexibility)
timeFrame: assessed in the phase 1, at visit nº 1 (10 minutes)
measure: Physical fitness (flexibility)
timeFrame: assessed in the phase 2 (only pregnant women), at visit nº 5 (10 minutes)
measure: Physical fitness (cardiorespiratory fitness)
timeFrame: assessed in the phase 1, at visit nº 1 (30 minutes)
measure: Physical fitness (cardiorespiratory fitness)
timeFrame: assessed in the phase 2 (only pregnant women), at visit nº 5 (30 minutes)
measure: Resting energy expenditure
timeFrame: assessed in the phase 1, at visit nº 1 (2 hours)
measure: Physical activity
timeFrame: assessed in the phase 1 - 10 continuous days
measure: Physical activity
timeFrame: assessed in the phase 2 (only pregnant women) - 10 continuous days
measure: Vital signs (systolic and diastolic blood pressure)
timeFrame: assessed in the phase 1, at visit nº 1 (15 minutes)
measure: Vital signs (systolic and diastolic blood pressure)
timeFrame: assessed in the phase 2 (only pregnant women), at visit nº 5 (15 minutes)
measure: Vital signs (resting heart rate)
timeFrame: assessed in the phase 1, at visit nº 1 (15 minutes)
measure: Vital signs (resting heart rate)
timeFrame: assessed in the phase 2 (only pregnant women), at visit nº 5 (15 minutes)
measure: Initial anamnesis (sociodemographic and clinical information)
timeFrame: assessed in the phase 1, at visit nº 1 (40 minutes)
measure: Sleep quality (questionnaire)
timeFrame: assessed in the phase 1, at visit nº 1 (20 minutes)
measure: Sleep quality (questionnaire)
timeFrame: assessed in the phase 2 (only pregnant women), at visit nº 5 (20minutes)
Locations:
city: Graz
country: Austria
facility: University of Graz
state: Styria
Study officials:
affiliation: University of Graz
name: Mireille NM van Poppel, Prof.
role: PRINCIPAL_INVESTIGATOR
References: