Clinical trial NCT06466967: Clinical Utility of Tight Objectives of Advanced Hybrid Closed-loop Systems Among Type 1 Diabetes Patients (TightT1AHCL)
Official title: Clinical Utility of a Tight Glucose Objectives Through Advanced Hybrid Closed-loop Systems in Adult Patients With Type 1 Diabetes and Poor Glycemic Control
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Type 1 Diabetes
Keywords: Type 1 Diabetes
advanced hybrid closed-loop
tight time in range
artificial pancreas
Lead sponsor: Castilla-La Mancha Health Service
Sponsor class: OTHER
First posted: 2024-06-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with type 1 diabetes and poor prior glycemic control, regardless previous treatment, attended in the Public Health System of Castilla-La Mancha in the Health Area of the Ciudad Real General University Hospital

Brief summary: Diabetes is a chronic disease with a relevant public health burden. Maintaining blood glucose levels as close to normal as possible is essential to avoid the associated microvascular and macrovascular complications. Therefore, the key to prevent and/or reduce the development of these chronic complications lies in an adequate and strict glycemic control.

This study consist of a prospective analytical clinical study in patients with type 1 diabetes (T1D). The main objective is to analyze the effect on time in range (TIR, 70-180 mg/dL) of interstitial glucose after switching to a tighter glucose objective in advanced hybrid closed-loop (AHCL) treated adult T1D patients previously treated with multiple dose insulin injection (MDI) or other AHCL systems without tighter glucose objective function.

Detailed description: Diabetes is a chronic disease with a relevant public health burden. T1D is characterized by the autoimmune destruction of insulin-producing pancreatic beta cells, which requires the administration of exogenous insulin for its treatment. Maintaining blood glucose levels as close to normal as possible is essential to avoid the associated microvascular and macrovascular complications that affect quality of life, as well as morbidity and mortality due to the deleterious long-term effects of suboptimal control. Therefore, the key to prevent and/or reduce the development of these complications lies in adequate and strict glycemic control.

On the one hand, the use of advanced hybrid closed-loop (AHCL) systems in patients with T1D is associated with improved glycemic control and quality of life in both controlled clinical trials and real-life studies. Since 2021, AHCL systems are considered the standard of care, ahead of traditional MDI. On the other hand, among the adjustment parameters of these systems, each AHCL offers different target levels of glycemic control. There is previous evidence that correlates the use of the more intense modes offered by each of the systems with substantial increases in TIR, improvement in the other glycometric variables, as well as the development of acute or chronic complications. In this regard, a new AHCL system has recently been introduced in Spain: CamAPS FX. It is the first AHCL system with the availability of setting lycemic control targets below the traditional 100 mg/dL limit. This system allows glycemic objective as low as 80 mg/dL.

However, there is no information on the benefits and safety of using tighter control targets. The main objective of this study is to analyze the effect on TIR after switching to a tighter glucose objective throught AHCL among adult T1D patients previously treated with MDI or other AHCL systems without this feature.

This is monocenter prospective analytical clinical study (non-randomized). The target population will be adult T1D patients not meeting glycemic control goals followed in Ciudad Real General University Hospital.

Eligibility criteria: Inclusion Criteria:

* Patients with type 1 diabetes.
* Age greater than or equal to 18 years.
* HbA1c \> 7% (previous poor glycemic control condition).
* Prior treatment with MDI or aHCL.

Exclusion Criteria:

* Other types of diabetes.
* Pregnancy or pre-conception control.
* Uncontrolled psychiatric disease.
* Current or previous treatment with CamAPS-Ypsopump.
* No glucometric data available during the periods under study.
* History of severe hypoglycemia.

Primary outcomes:
measure: Time in Range (TIR) differences
timeFrame: 3 months
Secondary outcomes:
measure: Time in Range (TIR) differencies among therapies
timeFrame: 3 months
measure: Differences between stringent glucose control targets
timeFrame: 3 months
measure: HbA1c differences
timeFrame: 3 months
measure: Usage of AHCL system
timeFrame: 3 months
measure: MCG adherence
timeFrame: 3 months
measure: Total daily insulin requirements
timeFrame: 3 months
measure: Basal daily insulin requirements
timeFrame: 3 months
measure: Bolus daily insulin requirements
timeFrame: 3 months
measure: Time in Tight Range (TTIR 70-140 mg/dL) differences
timeFrame: 3 months
measure: Time Above Range 1 (TAR-1 >180 mg/dL) differences
timeFrame: 3 months
measure: Time Above Range 2 (TAR-2 >250 mg/dL) differences
timeFrame: 3 months
measure: Time Below Range 1 (TBR-1 <70 mg/dL) differences
timeFrame: 3 months
measure: Time Below Range 2 (TBR-2 <54 mg/dL) differences
timeFrame: 3 months
measure: Episodes of hyperglycemia level 1 (nº of episodes >180 mg/dL).
timeFrame: 3 months
measure: Episodes of hyperglycemia level 2 (nº of episodes >250 mg/dL).
timeFrame: 3 months
measure: Episodes of hypoglycemia level 1 (nº of episodes <70 mg/dL).
timeFrame: 3 months
measure: Episodes of hypoglycemia level 2 (nº of episodes <54 mg/dL).
timeFrame: 3 months
measure: Nocturnal episodes of hypoglycemia
timeFrame: 3 months
measure: Glycemic variability
timeFrame: 3 months
measure: Mean interstitial glucose
timeFrame: 3 months
measure: Glucose management indicator (GMI)
timeFrame: 3 months
measure: Acute complications and mortality
timeFrame: 3 months
measure: Differences in the Percetage of patients fullfilling the International Consensus of Time in Range
timeFrame: 3 months
Other outcomes:
measure: Hypoglycemia Fear Survey (HFS questionnaire)
timeFrame: 3 months
measure: Diabetes Treatment Satisfaction Questionnaire (DTSQ)
timeFrame: 3 months
measure: Clarke's questionnaire
timeFrame: 3 months
measure: Quality-of-life questionnaire designed for diabetes mellitus (EsDQOL)
timeFrame: 3 months
Locations:
city: Ciudad Real
country: Spain
facility: Ciudad Real General University Hospital
Study officials:
References:
citation: Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, Bosi E, Buckingham BA, Cefalu WT, Close KL, Cobelli C, Dassau E, DeVries JH, Donaghue KC, Dovc K, Doyle FJ 3rd, Garg S, Grunberger G, Heller S, Heinemann L, Hirsch IB, Hovorka R, Jia W, Kordonouri O, Kovatchev B, Kowalski A, Laffel L, Levine B, Mayorov A, Mathieu C, Murphy HR, Nimri R, Norgaard K, Parkin CG, Renard E, Rodbard D, Saboo B, Schatz D, Stoner K, Urakami T, Weinzimer SA, Phillip M. Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range. Diabetes Care. 2019 Aug;42(8):1593-1603. doi: 10.2337/dci19-0028. Epub 2019 Jun 8.
citation: Bally L, Thabit H, Kojzar H, Mader JK, Qerimi-Hyseni J, Hartnell S, Tauschmann M, Allen JM, Wilinska ME, Pieber TR, Evans ML, Hovorka R. Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study. Lancet Diabetes Endocrinol. 2017 Apr;5(4):261-270. doi: 10.1016/S2213-8587(17)30001-3. Epub 2017 Jan 14.
citation: Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL Trial Research Group. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019 Oct 31;381(18):1707-1717. doi: 10.1056/NEJMoa1907863. Epub 2019 Oct 16.
citation: Bergenstal RM, Nimri R, Beck RW, Criego A, Laffel L, Schatz D, Battelino T, Danne T, Weinzimer SA, Sibayan J, Johnson ML, Bailey RJ, Calhoun P, Carlson A, Isganaitis E, Bello R, Albanese-O'Neill A, Dovc K, Biester T, Weyman K, Hood K, Phillip M; FLAIR Study Group. A comparison of two hybrid closed-loop systems in adolescents and young adults with type 1 diabetes (FLAIR): a multicentre, randomised, crossover trial. Lancet. 2021 Jan 16;397(10270):208-219. doi: 10.1016/S0140-6736(20)32514-9.
citation: Beato-Vibora PI, Chico A, Moreno-Fernandez J, Bellido-Castaneda V, Nattero-Chavez L, Picon-Cesar MJ, Martinez-Brocca MA, Gimenez-Alvarez M, Aguilera-Hurtado E, Climent-Biescas E, Azriel-Mir S, Rebollo-Roman A, Yoldi-Vergara C, Pazos-Couselo M, Alonso-Carril N, Quiros C. A Multicenter Prospective Evaluation of the Benefits of Two Advanced Hybrid Closed-Loop Systems in Glucose Control and Patient-Reported Outcomes in a Real-world Setting. Diabetes Care. 2024 Feb 1;47(2):216-224. doi: 10.2337/dc23-1355.
citation: El Malahi A, Van Elsen M, Charleer S, Dirinck E, Ledeganck K, Keymeulen B, Crenier L, Radermecker R, Taes Y, Vercammen C, Nobels F, Mathieu C, Gillard P, De Block C. Relationship Between Time in Range, Glycemic Variability, HbA1c, and Complications in Adults With Type 1 Diabetes Mellitus. J Clin Endocrinol Metab. 2022 Jan 18;107(2):e570-e581. doi: 10.1210/clinem/dgab688.