Clinical trial NCT05258292: Glycemic Variations During the Menstrual Cycle in Women With Type 1 Diabetes
Official title: Glycemic Variations During the Menstrual Cycle in Women With Type 1 Diabetes: the GLYMETY Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type1diabetes
Keywords: Menstrual cycle
Continuous glucose monitoring
Insulin dose
Physical activity
Food intake
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
First posted: 2022-02-28
Enrollment: 86
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women aged 18 to 50 living with type 1 diabetes.

Brief summary: In clinical practice, women living with type 1 diabetes frequently report that insulin requirements change across the menstrual cycle. Consequently, glycemic fluctuations are observed. This phenomenon could be explained by a decrease in insulin sensitivity during the second half of the menstrual cycle (luteal phase).

Overall, despite an important proportion of women reporting glycemic and/or insulin variations across the menstrual cycle, studies to date have involved small sample sizes, and have had inconsistent results. The objective of this study will be to study glycemic fluctuations across the menstrual cycle using CGM data, alongside insulin data, in a large sample of women.


Eligibility criteria: Inclusion Criteria:

1. Females aged 18 to 50 living in Canada.
2. Clinical diagnosis of type 1 diabetes or latent autoimmune diabetes in adults (LADA) for at least one year.
3. Using insulin pump therapy, multiple daily injections or automated insulin delivery systems for at least 3 months.
4. Using a continuous glucose monitoring (CGM) system.
5. Having at least one menses in the last 40 days.
6. Accepting to share CGM data with the research team and if applicable insulin pump data.This access will be limited to the study period.
7. Having a smartphone or tablet to follow menstrual cycles.
8. Stable weight (less than 5% variation in the last 3 months).

Exclusion Criteria:

1. Using a hormonal contraception method that eliminates menses (Depo Provera, progestin intrauterine device, extented-cycle regimen with birth control pill)
2. Using regular insulin (Entuzity U500, Novolin ge Toronto or Humulin R).
3. Clinically significant nephropathy (eGFR \< 30 ml/min/1.73m2, planned or on dialysis) or neuropathy (e.g., known uncontrolled gastroparesis) as judged by the investigator.
4. Recent (\< 6 months) acute macrovascular event (e.g., acute coronary syndrome or cardiac surgery).
5. Anticipated therapeutic change (including change of insulin type and/or type of CGM sensor, insulin pump or AID (automated insulin device) system) between admission and end of the study.
6. Anticipated change in contraception method or plan to begin or stop a contraceptive method.
7. Anticipated need to use acetaminophen during the study period at a dose above 1g every 6 hours.
8. Pregnancy (ongoing or current attempt to become pregnant)
9. Breastfeeding
10. Uncontrolled thyroid disease (TSH should be in target range and treatment stable for at least 6 weeks).
11. Severe hypoglycemic episode within two weeks of screening
12. Severe hyperglycemic episodes requiring hospitalization in the last 3 months.
13. Current use of glucocorticoid medication (except low stable dose and inhaled steroids and stable adrenal insufficiency treatment e.g., Cortef®)
14. Agents affecting gastric emptying (Motilium®, Victoza®, Ozempic®, Trulicity®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, Prandase®, DPP-4 inhibitors) unless at a stable dose for 3 months and without anticipated change during the study.
15. Current use of SGLT-2 inhibitors unless at a stable dose for at least 3 months, without anticipated change during the study and appropriate ketone testing is performed.
16. Other serious medical illnesses which likely interfere with study participation or with the ability to complete the study by the judgment of the investigator.
17. Anticipation of a significant change in exercise or diet regimen between admission and end of the study (i.e., starting or stopping an organized sport; planned significant diet change).
18. Anticipated radiologic examination incompatible with CGM wear for more than 10 days between admission and end of the study (e.g., repeated MRI).
19. In the opinion of the investigator, a participant who is unable or unwilling to complete the study.
20. If taking medication for hypothyroidism, no change of dose (Levothyroxin) in the last 6 weeks.

Primary outcomes:
measure: Mean glucose levels during the early follicular phase
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Mean glucose levels during the mid-late follicular phase
timeFrame: Day 6 until 2 days prior to ovulation
measure: Mean glucose levels during the periovulation phase
timeFrame: Ovulation plus/minus 1 day
measure: Mean glucose levels during the early luteal phase
timeFrame: Day 2 to 4 after ovulation
measure: Mean glucose levels during the mid-luteal phase
timeFrame: Day 5 to 9 after ovulation
measure: Mean glucose levels during the late luteal phase
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
Secondary outcomes:
measure: Percentage of time of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Percentage of time of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: Day 6 until 2 days prior to ovulation
measure: Percentage of time of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: Ovulation plus/minus 1 day
measure: Percentage of time of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: Day 2 to 4 after ovulation
measure: Percentage of time of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: Day 5 to 9 after ovulation
measure: Percentage of time of glucose levels between 3.9 and 7.8 mmol/L
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Percentage of time of glucose levels between 3.9 and 10.0 mmol/L
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Percentage of time of glucose levels between 3.9 and 10.0 mmol/L
timeFrame: Day 6 until 2 days prior to ovulation
measure: Percentage of time of glucose levels between 3.9 and 10.0 mmol/L
timeFrame: Ovulation plus/minus 1 day
measure: Percentage of time of glucose levels between 3.9 and 10.0 mmol/L
timeFrame: Day 2 to 4 after ovulation
measure: Percentage of time of glucose levels between 3.9 and 10.0 mmol/L
timeFrame: Day 5 to 9 after ovulation
measure: Percentage of time of glucose levels between 3.9 and 10.0 mmol/L
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Percentage of time of glucose levels below 3.9 mmol/L
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Percentage of time of glucose levels below 3.9 mmol/L
timeFrame: Day 6 until 2 days prior to ovulation
measure: Percentage of time of glucose levels below 3.9 mmol/L
timeFrame: Ovulation plus/minus 1 day
measure: Percentage of time of glucose levels below 3.9 mmol/L
timeFrame: Day 2 to 4 after ovulation
measure: Percentage of time of glucose levels below 3.9 mmol/L
timeFrame: Day 5 to 9 after ovulation
measure: Percentage of time of glucose levels below 3.9 mmol/L
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Percentage of time of glucose levels below 3.0 mmol/L
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Percentage of time of glucose levels below 3.0 mmol/L
timeFrame: Day 6 until 2 days prior to ovulation
measure: Percentage of time of glucose levels below 3.0 mmol/L
timeFrame: Ovulation plus/minus 1 day
measure: Percentage of time of glucose levels below 3.0 mmol/L
timeFrame: Day 2 to 4 after ovulation
measure: Percentage of time of glucose levels below 3.0 mmol/L
timeFrame: Day 5 to 9 after ovulation
measure: Percentage of time of glucose levels below 3.0 mmol/L
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: Day 6 until 2 days prior to ovulation
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: Ovulation plus/minus 1 day
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: Day 2 to 4 after ovulation
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: Day 5 to 9 after ovulation
measure: Percentage of time of glucose levels above 10.0 mmol/L
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Percentage of time of glucose levels above 13.9 mmol/L
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Percentage of time of glucose levels above 13.9 mmol/L
timeFrame: Day 6 until 2 days prior to ovulation
measure: Percentage of time of glucose levels above 13.9 mmol/L
timeFrame: Ovulation plus/minus 1 day
measure: Percentage of time of glucose levels above 13.9 mmol/L
timeFrame: Day 2 to 4 after ovulation
measure: Percentage of time of glucose levels above 13.9 mmol/L
timeFrame: Day 5 to 9 after ovulation
measure: Percentage of time of glucose levels above 13.9 mmol/L
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Standard deviation of glucose levels
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Standard deviation of glucose levels
timeFrame: Day 6 until 2 days prior to ovulation
measure: Standard deviation of glucose levels
timeFrame: Ovulation plus/minus 1 day
measure: Standard deviation of glucose levels
timeFrame: Day 2 to 4 after ovulation
measure: Standard deviation of glucose levels
timeFrame: Day 5 to 9 after ovulation
measure: Standard deviation of glucose levels
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Coefficient of variance of glucose levels
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Coefficient of variance of glucose levels
timeFrame: Day 6 until 2 days prior to ovulation
measure: Coefficient of variance of glucose levels
timeFrame: Ovulation plus/minus 1 day
measure: Coefficient of variance of glucose levels
timeFrame: Day 2 to 4 after ovulation
measure: Coefficient of variance of glucose levels
timeFrame: Day 5 to 9 after ovulation
measure: Coefficient of variance of glucose levels
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Low blood glucose index
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Low blood glucose index
timeFrame: Day 6 until 2 days prior to ovulation
measure: Low blood glucose index
timeFrame: Ovulation plus/minus 1 day
measure: Low blood glucose index
timeFrame: Day 2 to 4 after ovulation
measure: Low blood glucose index
timeFrame: Day 5 to 9 after ovulation
measure: Low blood glucose index
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: High blood glucose index
timeFrame: Day 1 to 5 of the menstrual cycle
measure: High blood glucose index
timeFrame: Day 6 until 2 days prior to ovulation
measure: High blood glucose index
timeFrame: Ovulation plus/minus 1 day
measure: High blood glucose index
timeFrame: Day 2 to 4 after ovulation
measure: High blood glucose index
timeFrame: Day 5 to 9 after ovulation
measure: High blood glucose index
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Standard deviation of insulin delivery
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Standard deviation of insulin delivery
timeFrame: Day 6 until 2 days prior to ovulation
measure: Standard deviation of insulin delivery
timeFrame: Ovulation plus/minus 1 day
measure: Standard deviation of insulin delivery
timeFrame: Day 2 to 4 after ovulation
measure: Standard deviation of insulin delivery
timeFrame: Day 5 to 9 after ovulation
measure: Standard deviation of insulin delivery
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Coefficient of variance of insulin delivery
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Coefficient of variance of insulin delivery
timeFrame: Day 6 until 2 days prior to ovulation
measure: Coefficient of variance of insulin delivery
timeFrame: Ovulation plus/minus 1 day
measure: Coefficient of variance of insulin delivery
timeFrame: Day 2 to 4 after ovulation
measure: Coefficient of variance of insulin delivery
timeFrame: Day 5 to 9 after ovulation
measure: Coefficient of variance of insulin delivery
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
measure: Total insulin delivery
timeFrame: Day 1 to 5 of the menstrual cycle
measure: Total insulin delivery
timeFrame: Day 6 until 2 days prior to ovulation
measure: Total insulin delivery
timeFrame: Ovulation plus/minus 1 day
measure: Total insulin delivery
timeFrame: Day 2 to 4 after ovulation
measure: Total insulin delivery
timeFrame: Day 5 to 9 after ovulation
measure: Total insulin delivery
timeFrame: Day 10 after ovulation until the first day of the next menstrual cycle
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Rémi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
References: