Clinical trial NCT06158503: Glycemic Control and Osteohealth in Adults Living With Type 1 Diabetes
Official title: GLYcemic COntrol and OSTEOhealth: Impact of Short-Term Glycemic Control on Skeletal Outcomes in Adults With Type 1 Diabetes
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type 1 Diabetes
Keywords: Type 1 Diabetes
Bone Health
Automated Insulin Delivery
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Laval University
name: Institut de Recherches Cliniques de Montreal
First posted: 2023-12-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People living with type 1 diabetes who do not use an automated insulin delivery system but wish to do so. The study takes place around the initiation of AID.

Brief summary: Bone damage is frequently observed in type 1 diabetes, and hyperglycemia is associated with an increased risk of fracture. This pilot study in 25 people living with type 1 diabetes aims to determine whether the introduction of an automated insulin delivery (AID) system improves bone markers through rapide optimization of glycemic control. Measurements will be taken before the start of AID, 2 months and 4 months afterwards.

Detailed description: Background: Bone damage is a frequently overlooked complication of type 1 diabetes (T1D), but significantly increases the risk of fractures as early as childhood. Fractures in individuals with T1D increase the risk of delayed healing, postoperative complications, loss of autonomy, reduced quality of life and even mortality. The pathophysiology of bone alterations in T1D probably differs from that of primary osteoporosis. Studies show lower bone mineral density in T1D, but this is not sufficient to fully explain the risk of fractures. T1D is also characterized by low bone remodeling and altered bone microarchitecture. Although chronic hyperglycemia is a risk factor for fracture in T1DM, the effect of improved glycemic control on bone markers remains unclear. The main hypothesis is that rapid optimization of the glycemic profile (hyperglycemia and variability) may improve bone remodeling in people living with T1DM who have suboptimal glycemic control.

Aim: The primary objective of this pilot study is to quantify the proportion of participants significantly increasing at least one of the serum markers of bone remodeling post-installation of an automated insulin delivery system.

Secondary objectives are to quantify: 1) the magnitude of change in each of the serum markers of bone remodeling pre-intervention and at 2 and 4 months post-intervention; 2) the efficacy of the automated insulin delivery system in terms of glycemic control and variability (mean change in HbA1c and glycemic parameters derived from the continuous glucose monitoring system).

Methods: method: This is a prospective pilot study involving 25 adults aged 18 and over living with T1DM or latent autoimmune diabetes of adults (LADA) who are interested in starting an automated insulin delivery system (artificial pancreas).

This study will involve 3 visits:

1. Visit 1: before installation of the automated insulin delivery system,
2. Visit 2: follow-up at 2 months after installation of the automated insulin delivery system,
3. Visit 3: follow-up at 4 months after installation of the automated insulin delivery system.

During visits 1 and 3, participants will take a blood sample, perform a brief physical examination and complete questionnaires.

During visit 1, participants will also undertake a urine sample, and the research team will conduct a brief interview to obtain information on their diabetes diagnosis, associated complications, and medication use.

During Visit 2: blood sample only.

The project will not interfere with the participant's diabetes management. They will be asked to share a copy of their 14-day continuous glucose monitoring profile during the visit periods.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years;
* Diagnosis of T1D or latent autoimmune diabetes of adults (LADA) for at least one year;
* Current HbA1c \>8.0% and high glycemic variability (CV \>36.0% using CGM);
* Participant planning to start using one of the commercially available AID;
* Anticipated use of the closed-loop mode;
* Willing to share CGM data during the study period.

Exclusion Criteria:

* Woman who was pregnant, gave birth or breastfed less than 6 months before the beginning of the study or who plans to become pregnant during the study;
* Conditions affecting bone turnover markers, such as chronic kidney disease (estimated GFR \<30 ml/min), liver disease, intestinal malabsorption including celiac disease, organ transplant, active cancer, rheumatoid arthritis, and endocrinopathies (active hyperthyroidism, uncontrolled hypothyroidism with abnormal TSH, parathyroid disease, hypogonadism, Cushing syndrome, adrenal insufficiency and acromegaly);
* Anticipated therapeutic change and/or type of CGM sensor, insulin pump, or AID during the study period;
* Anticipated need to use acetaminophen during the study period at a dose above 1g every 6 hours;
* Current or anticipated use of hydroxyurea;
* Intake in the past 12 months of drugs influencing bone turnover markers, such as oral or intra-articular glucocorticoids (≥ 7.5 mg daily Prednisone or equivalent during ≥ 3 months or ≥ four intra-articular glucocorticoid infiltrations in the past year), aromatase inhibitor therapy for breast cancer and anti-androgen therapy for prostate cancer, anticoagulants, SGLT-2 inhibitors, thiazolidinediones, and anti-osteoporosis drugs;
* Unable to consent.

Primary outcomes:
measure: Bone remodeling improvement
timeFrame: 4 months
Secondary outcomes:
measure: Carboxy-terminal collagen crosslinks change
timeFrame: 2 months
measure: Carboxy-terminal collagen crosslinks change
timeFrame: 4 months
measure: N-terminal propeptide (P1NP) change
timeFrame: 2 months
measure: N-terminal propeptide (P1NP) change
timeFrame: 4 months
measure: Osteocalin change
timeFrame: 2 months
measure: Osteocalin change
timeFrame: 4 months
measure: HbA1c change
timeFrame: 2 months
measure: HbA1c change
timeFrame: 4 months
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: CHUM
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
Study officials:
affiliation: IRCM
name: Rémi Rabasa-Lhoret, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: