Maternal ExeRcIse Timing to Optimise Postprandial Glucose in Type 1 Diabetes

Type 1 Diabetes Clinical Trial

— MERIT1D  

Official title:

Maternal ExeRcIse Timing to Optimise Postprandial Glucose in Type 1 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05843175
• Other study ID #: 11954
• Status: Recruiting
• Phase: N/A
• Start date: June 22, 2023
• Est. completion date: April 24, 2025

Study information

• Verified date: March 2024
• Source: University of Graz
• Contact: Mireille NM van Poppel, Prof.
• Phone: +43 (0)316 380 - 1022
• Email: mireille.van-poppel[@]uni-graz.at
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: April 24, 2025
• Est. primary completion date: September 24, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Pregnancy in Diabetic
• Pregnancy in Diabetics
• Type 1 Diabetes

Intervention

Other:
• Exercise and meal testing (acute stimuli)
Pre-meal exercise: 1º milkshake intake + 2º exercise test Post-meal exercise: 1º exercise test + 2º milkshake intake Non-exercise meal: Only milkshake intake

Locations

Country	Name	City	State
Austria	University of Graz	Graz	Styria

Sponsors (2)

Lead Sponsor	Collaborator
University of Graz	Medical University of Graz

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Placenta completeness	The number of present and missing cotyledons and velamentous vessels will be examined visually in all the quadrants.	assessed at birth - 20 minutes
Other	Neonate height	Neonate height (cm)	assessed at birth - 5 minutes
Other	Neonate ponderal index	Neonate weight/height ratio: 100 x weight / (Height)3	estimated after birth - 3 minutes
Other	Neonate anthropometrics	Neonate head and abdomen circumference (cm). These circumferences will be measured using a stretch-resistant measuring tape.	assessed at birth - 10 minutes
Other	Neonate Apgar score	Neonate Apgar score (1-10). The higher score is indicative of a better health status of the newborn after birth	assessed at birth - 5 minutes
Other	Small for gestational age	Newborns will be diagnosed as small for gestational age newborns if their birth weight is lower than the 10th percentile for their gestational age	assessed after birth - 5 minutes
Other	Large for gestational age	Newborns will be diagnosed as large for gestational age newborns if their birth weight is greater than the 90th percentile for their gestational age	assessed after birth - 5 minutes
Other	Physical fitness (muscle strenght)	Upper body muscle strength will be measured by the handgrip strength test.	assessed in the phase 1, at visit nº 1 (10 minutes)
Other	Physical fitness (muscle strenght)	Upper body muscle strength will be measured by the handgrip strength test.	assessed in the phase 2 (only pregnant women), at visit nº 5 (10 minutes)
Other	Physical fitness (flexibility)	Upper body flexibility will be assessed by the back scratch test, measuring the distance or overlap between the middle fingers of both hands behind the back.	assessed in the phase 1, at visit nº 1 (10 minutes)
Other	Physical fitness (flexibility)	Upper body flexibility will be assessed by the back scratch test, measuring the distance or overlap between the middle fingers of both hands behind the back.	assessed in the phase 2 (only pregnant women), at visit nº 5 (10 minutes)
Other	Physical fitness (cardiorespiratory fitness)	Cardiorespiratory fitness will be assessed using a submaximal walking treadmill test while recording gas exchange data (breath by breath system).	assessed in the phase 1, at visit nº 1 (30 minutes)
Other	Physical fitness (cardiorespiratory fitness)	Cardiorespiratory fitness will be assessed using a submaximal walking treadmill test while recording gas exchange data (breath by breath system).	assessed in the phase 2 (only pregnant women), at visit nº 5 (30 minutes)
Other	Resting energy expenditure	Gas exchange will be measured breath by breath using a portable gas analyser	assessed in the phase 1, at visit nº 1 (2 hours)
Other	Physical activity	Physical activity levels will be measured with triaxial accelerometry.	assessed in the phase 1 - 10 continuous days
Other	Physical activity	Physical activity levels will be measured with triaxial accelerometry.	assessed in the phase 2 (only pregnant women) - 10 continuous days
Other	Vital signs (systolic and diastolic blood pressure)	Systolic and diastolic blood pressure (mmHg) will be assessed twice using an upper arm digital sphygmomanometer with women seated, relaxed and not talking.	assessed in the phase 1, at visit nº 1 (15 minutes)
Other	Vital signs (systolic and diastolic blood pressure)	Systolic and diastolic blood pressure (mmHg) will be assessed twice using an upper arm digital sphygmomanometer with women seated, relaxed and not talking.	assessed in the phase 2 (only pregnant women), at visit nº 5 (15 minutes)
Other	Vital signs (resting heart rate)	Resting heart rate (beats per minute) will be assessed twice using an upper arm digital sphygmomanometer with women seated, relaxed and not talking.	assessed in the phase 1, at visit nº 1 (15 minutes)
Other	Vital signs (resting heart rate)	Resting heart rate (beats per minute) will be assessed twice using an upper arm digital sphygmomanometer with women seated, relaxed and not talking.	assessed in the phase 2 (only pregnant women), at visit nº 5 (15 minutes)
Other	Initial anamnesis (sociodemographic and clinical information)	Relevant information from the patients will be collected by the physicians who will ask them, and by an initial questionnaire prepared by the researchers (e.g., age, educational level, occupational status, medications, diseases, etc.).	assessed in the phase 1, at visit nº 1 (40 minutes)
Other	Sleep quality (questionnaire)	The sleep quality will be assessed using a validated questionnaire, the Pittsburgh Sleep Quality Index questionnaire (PSQI). Higher scores indicate worse sleep quality (0-21).	assessed in the phase 1, at visit nº 1 (20 minutes)
Other	Sleep quality (questionnaire)	The sleep quality will be assessed using a validated questionnaire, the Pittsburgh Sleep Quality Index questionnaire (PSQI). Higher scores indicate worse sleep quality (0-21).	assessed in the phase 2 (only pregnant women), at visit nº 5 (20minutes)
Primary	Percentage of time spent in the euglycemic range for the 24 hours after each experimental condition	T1DM non-pregnant women, euglycemic range: 3.9 - 10 mmol/L (70 - 180 mg/dL).; T1DM pregnant women, euglycemic range: 3.5 - 7.8 mmol/L (63 - 140 mg/dL).	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Primary	Percentage of time spent in the euglycemic range for the 24 hours after each experimental condition	T1DM non-pregnant women: 3.9 - 10 mmol/L (70 - 180 mg/dL).; T1DM pregnant women: 3.5 - 7.8 mmol/L (63 - 140 mg/dL).	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary	Percentage of time spent in hypoglycemia for the 24 hours after each experimental condition	T1DM non-pregnant women - range: < 3.9 mmol/L (< 70 mg/dL).; T1DM pregnant women - range: < 3.5 mmol/L (< 63 mg/dL).	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Secondary	Percentage of time spent in hypoglycemia for the 24 hours after each experimental condition	T1DM non-pregnant women - range: < 3.9 mmol/L (< 70 mg/dL).; T1DM pregnant women - range: < 3.5 mmol/L (< 63 mg/dL).	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary	Percentage of time spent in hyperglycemia for the 24 hours after each experimental condition	T1DM non-pregnant women - range: > 10 mmol/L (> 180 mg/dL).; T1DM pregnant women - range: > 7.8 mmol/L (> 140 mg/dL).	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Secondary	Percentage of time spent in hyperglycemia for the 24 hours after each experimental condition	T1DM non-pregnant women - range: > 10 mmol/L (> 180 mg/dL).; T1DM pregnant women - range: > 7.8 mmol/L (> 140 mg/dL).	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary	Differences in postprandial glucose levels 1-, 2-, and 4-hours post-experiment	Within-change in glucose values (mmol/L) from pre-experiment (before starting exercise/meal testing) to post-experiment (i.e., 1-, 2-, and 4-hours after starting exercise/meal intake) in each experimental day	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 4 h/day)
Secondary	Differences in postprandial glucose levels 1-, 2-, and 4-hours post-experiment	Within-change in glucose values (mmol/L) from pre-experiment (before starting exercise/meal testing) to post-experiment (i.e., 1-, 2-, and 4-hours after starting exercise/meal intake) in each experimental day	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 4 h/day)
Secondary	Number of hypoglycaemic events for the 24 hours after each experimental condition	T1DM non-pregnant women - range: < 3.9 mmol/L (< 70 mg/dL).; T1DM pregnant women - range: < 3.5 mmol/L (< 63 mg/dL).	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Secondary	Number of hypoglycaemic events for the 24 hours after each experimental condition	T1DM non-pregnant women - range: < 3.9 mmol/L (< 70 mg/dL).; T1DM pregnant women - range: < 3.5 mmol/L (< 63 mg/dL).	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary	Number of hyperglycaemic events for the 24 hours after each experimental condition	T1DM non-pregnant women - range: > 10 mmol/L (> 180 mg/dL).; T1DM pregnant women - range: > 7.8 mmol/L (> 140 mg/dL).	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Secondary	Number of hyperglycaemic events for the 24 hours after each experimental condition	T1DM non-pregnant women - range: > 10 mmol/L (> 180 mg/dL).; T1DM pregnant women - range: > 7.8 mmol/L (> 140 mg/dL).	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary	Percentage of time spent in nocturnal euglycemia within each experimental day	T1DM non-pregnant women - range: euglycemia 3.9 - 10 mmol/L (70 - 180 mg/dL).; T1DM pregnant women - range: euglycaemia 3.5 - 7.8 mmol/L (63 - 140 mg/dL).	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 00:00 am - 05:59 am)
Secondary	Percentage of time spent in nocturnal euglycemia within each experimental day	T1DM non-pregnant women - range: euglycemia 3.9 - 10 mmol/L (70 - 180 mg/dL).; T1DM pregnant women - range: euglycaemia 3.5 - 7.8 mmol/L (63 - 140 mg/dL).	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 )
Secondary	Percentage of time spent in diurnal euglycemia within each experimental day	T1DM non-pregnant women - range: euglycemia 3.9 - 10 mmol/L (70 - 180 mg/dL).; T1DM pregnant women - range: euglycaemia 3.5 - 7.8 mmol/L (63 - 140 mg/dL).	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 6.00 am - 23:59 am)
Secondary	Percentage of time spent in diurnal euglycemia within each experimental day	T1DM non-pregnant women - range: euglycemia 3.9 - 10 mmol/L (70 - 180 mg/dL).; T1DM pregnant women - range: euglycaemia 3.5 - 7.8 mmol/L (63 - 140 mg/dL).	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)
Secondary	Area under the curve of glycaemic exposure	Area under the curve of glycaemic exposure during the 2, 4 and 8 hours after meal intake at each experimental condition.	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 8 hours/day)
Secondary	Area under the curve of glycaemic exposure	Area under the curve of glycaemic exposure during the 2, 4 and 8 hours after meal intake at each experimental condition.	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 8 h/day)
Secondary	Glycaemic variability (standard deviation)	Standard deviation (SD) of the mean continuous glucose monitoring levels over the 24 hours after each experimental condition	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Secondary	Glycaemic variability (standard deviation)	Standard deviation (SD) of the mean continuous glucose monitoring levels over the 24 hours after each experimental condition	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary	Glycaemic variability (coefficient of variation)	Coefficient of variation of glucose levels over the 24 hours after each experimental condition	assessed in the study phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 24 hours/day)
Secondary	Glycaemic variability (coefficient of variation)	Coefficient of variation of glucose levels over the 24 hours after each experimental condition	assessed in the study phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 24 h/day)
Secondary	Maternal glucose metabolism	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to the glucose-insulin axis will be analysed (i.e., glucose, insulin, C-peptide and HbA1c).	assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
Secondary	Maternal glucose metabolism	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to the glucose-insulin axis will be analysed (i.e., glucose, insulin, C-peptide and HbA1c).	assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
Secondary	Maternal lipid profile	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to the lipid profile will be analysed (i.e., total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL-cholesterol, triglycerides and free fatty acids).	assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
Secondary	Maternal lipid profile	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to the lipid profile will be analysed (i.e., total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL-cholesterol, triglycerides and free fatty acids).	assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
Secondary	Maternal inflammatory markers	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to inflammatory-immunological responses will be analysed (e.g., IL-6, IL-8, IL-1ß, TNFa, C-reactive protein, IFN?)	assessed in the phase 1 (10 days) - at visit nº 2, 3, 4 (3 days, 3 h/day)
Secondary	Maternal inflammatory markers	Fasting and post-experiment blood samples will be collected using venous puncture in the antecubital vein. Metabolic markers related to inflammatory-immunological responses will be analysed (e.g., IL-6, IL-8, IL-1ß, TNFa, C-reactive protein, IFN?)	assessed in the phase 2 (only pregnant women, 10 days) - at visit nº 6, 7, 8 (3 days, 3 h/day)
Secondary	Placenta weight	Placenta weight (grams)	assessed at birth - 30 minutes
Secondary	Placenta biopsies	Eight biopsies will be collected, four on the maternal site and four on the fetal side. Relevant placental proteins (growth factors and cytokines) related to insulin signalling, glucose metabolism, and inflammation will be analysed (e.g., GM-CSF, GCSF, MCP1, TNF-a, IL-6, EGF, IFN-?, IL-8, IL-10, IL-1ß).	collected at birth - 1 hour
Secondary	Neonate weight	Neonate weight (grams)	assessed at birth - 5 minutes
Secondary	Placenta efficiency	Neonate weight divided by placenta weight	estimated after birth - 3 minutes