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The sponsor has temporarily suspended participant enrollment due to operational constraints impacting study implementation. This decision is not related to safety concerns. The study is expected to resume once the identified issues are addressed.
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Type 1 diabetes (T1D) affects around 200,000 people in France. The only treatment is insulin, administered either by multiple injections, by pump alone or, more recently, by automated insulin delivery systems (AIDs), which have resulted in a very significant improvement in glycaemic control and quality of life. These closed-loop (CL) devices are capable of effectively regulating the conventional factors associated with glycaemic disturbance, namely dietary intake and physical activity. However, they do not account of stress, which some subjects with T1D perceive as a major disrupter of their blood sugar levels. One of the reasons for this is undoubtedly that stress, unlike diet or physical activity, cannot be anticipated. Since stress is difficult to predict, it is also more difficult to study. Its onset, intensity, duration and progression are linked to the subject's experience, psychological state and environment. Not all patients respond to stress triggers in the same way. Some patients appear to be more reactive than others to these agents, particularly when they are exposed to them chronically or repeatedly, in an anxiety-provoking environment. This is known as chronic psychosocial stress, and it is this type of stress that seems to be most closely associated with glycaemic disturbance in subjects with T1D, most often in the form of hyperglycaemia and, more rarely, hypoglycaemia. However, there are no solid epidemiological or experimental data to support these observations.
The study we propose is a prospective multicentre clinical trial in 125 subjects with T1D treated with insulin pumps or multi-injections at 14 French university centres. Our aim is to evaluate the relationship between interstitial glucose levels measured by CGM and perceived stress, assessed 4 times a day, away from mealtimes in order to avoid the impact of dietary glycaemia, using a "stressometer". This stressometer is an application designed by CERITD that can be downloaded to the patient's smartphone and consists of an electronic visual analogue scale (VAS) on which the level of stress felt is evaluated quantitatively (continuous value between 0 and 10).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Visual analog scale to measure stress levels | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Assess stress levels 4 times a day before meals (morning, noon and evening and at bedtime) using a visual analogue scale | Behavioral | In addition to stress assessment with the stress meter, patients will be fitted with a Continious Glucose Monitoring |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between perceived daily stress, self-assessed on a multi-daily basis using a mobile subjective stress assessment application called a "stress meter", and blood glucose levels measured by continuous glucose monitoring (CGM) | Visual analogue scale to assess stress levels: 0: I feel absolutely no stress 10: I feel extremely stressed | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| HbA1c measurement | HbA1c measurement at inclusion | At Inclusion |
| Characterization of 4 patient profiles according to the impact of daily stress on glycemic control | Questionnaire for Assessing the Impact of Stress on Blood Sugar Levels. This questionnaire was designed and developed by CERITD to assess the impact of perceived stress on blood glucose levels in T1DM patients. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sylvia Franc, MD | Centre d'Etudes et de Recherche pour l'Intensification du Traitement du Diabète | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Angers University Hospital | Angers | 49100 | France | |||
| Avignon Hospital |
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| At inclusion |
| Number of days the Continuous subcutaneous Glucose Monitoring (CGM) worn | 14 days |
| Percentage of time the CGM is active (recommended at least 70% of the time) | 14 days |
| Percentage of sensor time in glucose level measured by the Dexcom One+ CGM time |
| 14 days |
| Variability of the CGM glucose level | The glycemic variation coefficient (CV) intra patient CV≤36%, CV > 36% | 14 days |
| Glucose management Indicator (GMI) | 14 days |
| Average CGM glucose level | Measurement of glucose by CGM | 14 days |
| Glycaemic evolution over a period during which stress is measured. | Measurement of the area under the curve (AUC) for blood glucose | 14 days |
| Glycaemic evolution over a period during which stress is measured. | Measurement of the maximum blood sugar | 14 days |
| Glycaemic evolution over a period during which stress is measured. | Measurement of the blood sugar delta | 14 days |
| Glycaemic evolution over a period during which stress is measured. | Measurement of the blood sugar average | 14 days |
| Measuring heart rate with the Empatica EmbracePlus watch | 14 days |
| Measuring heart rate variability with the Empatica EmbracePlus watch | 14 days |
| Measuring electrodermal activity with the Empatica EmbracePlus watch | 14 days |
| Measuring heart rate with the Oura ring | 14 days |
| Measuring heart rate variability with the Oura ring | 14 days |
| Measuring accelerometry parameters with the Empatica EmbracePlus watch | 14 days |
| Measuring accelerometry parameters with the Oura ring | 14 days |
| Measuring the amount of sleep you get with the Empatica EmbracePlus watch | "Sleep detection" parameter | 14 days |
| Measuring the amount of sleep you get with the Oura ring | sleep score | 14 days |
| Measuring total sleep time with the Oura ring | 14 days |
| Assessment of sleep quality | Visual Analogue Sleep Scale filled in each morning with reference to the previous night 0: I slept very badly 10: I slept very well | 14 days |
| Measurement of sleep characteristics with the Oura ring | Sleep efficiency as a percentage | 14 days |
| Measurement of inflammatory biomarkers | at inclusion and after 14 days |
| Capillary cortisol measurement | Hair cortisol levels measured at the end of study. | After 14 days |
| Assessment of diabetes-related distress in the test population . | PAID (Problem Areas in Diabetes) is a self-administered 5-item scale. Each item is scored from 0 (not a problem) to 4 (serious problem). | at inclusion |
| Assessment of stress levels using the STAI questionnaire | State-Trait Anxiety Inventory (STAI)-Y1: The STAI-Y1 is composed of 20 items. This questionnaire assesses how the patient feels at the present moment. Patients are asked to score each question on a four-point scale (from 1 -corresponding to "not at all" to 4 - "much"). | At inclusion and after 14 days |
| Assessment of stress levels using the STAI questionnaire | State-Trait Anxiety Inventory STAI-Y2 (anxiety score): The STAI-Y2 is composed of 20 items. This questionnaire assesses how the patient feels in general. Patients are asked to answer each question on a four-point scale (from 1 - corresponding to "almost never" to 4 -"almost always") | After 14 days |
| Assessment of diabetes-related distress in the test population . | DDS T1 is an indicator of overall diabetes distress (average of 17 items, rated 1 to 6 on a scale). A higher score indicates higher distress. | at inclusion and after 14 days |
| Evaluation of the perception of hypoglycaemia in the population tested with Clarke score | The Clarke questionnaire is comprised of eight questions to evaluate the hypoglycemia awareness. The answer for each individual question will represent a score (0 or 1). These scores will be summed together to a final score from 0 to 7, representing from normal to minimal/no hypoglycemia awareness. | at inclusion |
| Evaluation of the perception of hypoglycaemia in the population tested with Gold score | The Gold method is used to assess impaired awareness of hypoglycemia. The scale is from 1 to 7. A score of 4 or more indicates impaired awareness of hypoglycemia | at inclusion |
| Assessment of stress levels using the PSS-14 questionnaire (Perceived Stress Scale 14) | It is a five-point Likert-type scale and consists of 14 items. Participants rate each item on a scale ranging from "Never (0)" to "Very often (4)". Seven of the items with positive statements are scored in reverse. As the scores obtained from the scale increase, the perceived stress level of the person increases. PSS-14 scores range from 0 to 56, with 0-35 point range indicating normal stress level, 35-56 point range indicating that the individual is under stress | at inclusion and after 14 days |
| Assessment of stress levels : depression score | The Depression, Anxiety and Stress Scale 21 (DASS-21) is an inventory that will be used to identify the presence and intensity of depressive, anxiety and stress. For depression the cutoff scores are: Normal: 0-9, Mild: 10-12, Moderate:13-20, Severe: 21-27, and Extremely severe: 28-42. | After 7 days |
| Assessment of stress levels : anxiety score | The Depression, Anxiety and Stress Scale 21 (DASS-21) is an inventory that will be used to identify the presence and intensity of depressive, anxiety and stress. For anxiety the cutoff scores are: Normal: 0-6, Mild: 7-9, Moderate: 10-14, Severe:15-19, and Extremely severe: 20-42. | After 7 days |
| Assessment of stress levels : stress score | The Depression, Anxiety and Stress Scale 21 (DASS-21) is an inventory that will be used to identify the presence and intensity of depressive, anxiety and stress. For stress the cutoff scores are: Normal: 0-10, Mild:11-18, Moderate:19-26, Severe: 27-34, and Extremely severe: 35-42. | After 7 days |
| Diagnosis and measurement of the severity of depression: Patient Health Questionnaire (PHQ-9) | The Patient Health Questionnaire (PHQ-9) will be used to assess depressive symptoms, including suicidal ideation, over the last two weeks (9 questions). Items are scored 0-3, resulting in a total score of 0-27. Higher scores indicate more symptoms of depression. | After 7 days |
| Personality traits : Big Five Inventory 10 (BFI-10) | Items range from 1 (strongly approves) to 5 (strongly disapproves). Scales: openness to experience, conscientiousness, extraversion, agreeableness and neuroticism | After 7 days |
| Bortner scale | The Bortner self-assessment questionnaire consists of 14 items. It is used to classify individuals according to types of behaviour (A and B) | After 7 days |
| Quality of life assessment: Short Form 36 questionnaire (SF-36) | Short Form 36 (SF-36) -ranges between 0 (maximum disability) and 100 (no disability). The SF36 score can be converted to utility scores using values within the questionnaire. | After 14 days |
| Assessment of sleep quality: Pittsburgh Sleep Quality Index (PSQI) | Pittsburgh Sleep Quality Index (PSQI), a self-report questionnaire comprising seven component scores (subjective sleep quality, sleep latency, duration of sleep, sleep efficiency habits, sleep disturbances, use of sleeping medication, and daytime dysfunction), is used to evaluate sleep quality over the last month | After 14 days |
| Avignon |
| 84000 |
| France |
| Bordeaux University Hospital | Bordeaux | 33075 | France |
| Brest University Hospital | Brest | 29200 | France |
| Dijon University Hospital | Dijon | 21079 | France |
| CERITD (Centre d'Etudes et de Recherches pour l'Intensification du Traitement du Diabète) | Évry | 91058 | France |
| Grenoble University Hospital | Grenoble | 38043 | France |
| St Louis Hospital | La Rochelle | 17000 | France |
| Lille University Hospital | Lille | 59037 | France |
| DiabeCare diabetes centre | Lyon | 69008 | France |
| European Hospital | Marseille | 13003 | France |
| Private practice in endocrinology and metabolic diseases | Mérignac | 33700 | France |
| Rennes University Hospital | Rennes | 35200 | France |
| Strasbourg University Hospital | Strasbourg | 67091 | France |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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