Impact on the Oxidative Stress of the Different Analogues of Insulin in People With Type 1 Diabetes. (Ineox Study)

Study Overview
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Brief Summary
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This study evaluates in a group of people with DM 1 the influence in parameters of oxidative stress of the treatments with the different current analogs of insulin

Detailed Description
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To evaluate by a randomized study in a group of people with DM 1 the influence in parameters of oxidative stress of the treatments with the different current analogs of Insulin by analyzing: - The circulating levels of oxidative stress markers: A) Anti oxidation: Total antioxidant capacity (CAT), B) Oxidation: 8-iso-prostaglandin F2 alpha (8-iso-PGF2α), acid reactive substances Thiobarbituric (TBARS) and LDL-oxidized. - The relationship between glycemic control variables (HbA1c and mean glycemia) and variability (Standard deviation (SD), coefficient of variation (CV), and MAGE (mean amplitude of Glycemic excursions) and oxidative stress parameters analyzed. Goal 2: Study the activation of cellular pathways associated with processes and oxidation states, by means of a Array of expression of up to 50 genes encoding oxidative stress response genes as CPT1a (Carnitine Palmitoyl Transferase 1a, mitochondrial oxidizing b limiting enzyme), TAS (Fatty acyl synthetase), acetyl-coA carboxylase, Acadm (medium chain acyl dehydrogenase), Acadl (long chain acyl dehydrogenase), Acadvl (long chain acyl coA dehydrogenase), SOD1, Hmox1 and Glutamine-Cysteine ligase (Gclc).

Official Title
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Impact on the Oxidative Stress of the Different Analogues of Insulin in People With Type 1 Diabetes. Clinical Trial of Low Level of Intervention. (Ineox Study)

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Toujeo SoloStar
* Drug: Tresiba
* Drug: Humalog Kwikpen
* Drug: NovoRapid
* Drug: Apidra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 years and 65 years (inclusive). DM1 of more than two years of evolution with habitual follow-up in the Diabetes Unit of the University Regional Hospital of Malaga. HbA1c ≤ 10% Intensive treatment with basal MDI - Bowl for more than 12 months prior to the start of study. Gives informed consent. Exclusion Criteria: Chronic kidney disease, liver disease, thyroid dysfunction (except hypothyroidism correctly treated and controlled). Pregnancy or pregnancy planning. Diabetes mellitus type 2. Hyperuricemia (uric acid ≥7 mg / dl at the time of inclusion or current treatment With allopurinol). Absence of collaboration (informed consent).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tresiba & NovoRapid<br>Patients treated with Tresiba insulin and NovoRapid insulin | Drug: Tresiba<br>* Basal insulin at 16.00h and optimization of this basal doses with objetives of glycaemia before breakfast betwen 80-130 mg/ dl.<br>* Other names: Degludec insulin;Drug: NovoRapid<br>* Ultrarrapid insulin that the patient had already and dose adjustement to obtain postprandial glycaemia levels < 150 mg/dl<br>* Other names: Aspart insulin;|
| Other: Toujeo SoloStar & NovoRapid<br>Patients treated with Toujeo SoloStar insulin and NovoRapid insulin | Drug: Toujeo SoloStar<br>* Basal insulin at 16.00h and optimization of this basal doses with objetives of glycaemia before breakfast betwen 80-130 mg/ dl.<br>* Other names: Glargina U300;Drug: NovoRapid<br>* Ultrarrapid insulin that the patient had already and dose adjustement to obtain postprandial glycaemia levels < 150 mg/dl<br>* Other names: Aspart insulin;|
| Other: Tresiba & Humalog Kwikpen<br>Patients treated with Tresiba insulin and Humalog kwikpen insulin | Drug: Tresiba<br>* Basal insulin at 16.00h and optimization of this basal doses with objetives of glycaemia before breakfast betwen 80-130 mg/ dl.<br>* Other names: Degludec insulin;Drug: Humalog Kwikpen<br>* Ultrarrapid insulin that the patient had already and dose adjustement to obtain postprandial glycaemia levels < 150 mg/dl<br>* Other names: Lispro insulin;|
| Other: Toujeo SoloStar & Humalog Kwikpen<br>Patients treated with Toujeo SoloStar insulin and Humalog kwikpen insulin | Drug: Toujeo SoloStar<br>* Basal insulin at 16.00h and optimization of this basal doses with objetives of glycaemia before breakfast betwen 80-130 mg/ dl.<br>* Other names: Glargina U300;Drug: Humalog Kwikpen<br>* Ultrarrapid insulin that the patient had already and dose adjustement to obtain postprandial glycaemia levels < 150 mg/dl<br>* Other names: Lispro insulin;|
| Other: Tresiba & Apidra<br>Patients treated with Tresiba insulin and Apidra insulin | Drug: Tresiba<br>* Basal insulin at 16.00h and optimization of this basal doses with objetives of glycaemia before breakfast betwen 80-130 mg/ dl.<br>* Other names: Degludec insulin;Drug: Apidra<br>* Ultrarrapid insulin that the patient had already and dose adjustement to obtain postprandial glycaemia levels < 150 mg/dl<br>* Other names: Glulisine insulin;|
| Other: Toujeo SoloStar & Apidra<br>Patients treated with Toujeo SoloStar insulin and Apidra insulin | Drug: Toujeo SoloStar<br>* Basal insulin at 16.00h and optimization of this basal doses with objetives of glycaemia before breakfast betwen 80-130 mg/ dl.<br>* Other names: Glargina U300;Drug: Apidra<br>* Ultrarrapid insulin that the patient had already and dose adjustement to obtain postprandial glycaemia levels < 150 mg/dl<br>* Other names: Glulisine insulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxidative stress markers with the new slow insulin analogues | To evaluate the impact on the circulating levels of oxidative stress markers of the different treatments using the new slow insulin analogues. 1a) Anti oxidation: Total antioxidant capacity (CAT), and 1b) Oxidation: 8-iso-prostaglandin F2 alpha (8-iso-PGF2α), thiobarbituric acid reactive substances (TBARS) and LDL-oxidized | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c | Glycemic control: glycosylated hemoglobin | 6 month | 
| Mean blood glucose | Glycemic control: mean blood glucose (mg/dl) | 6 month | 
| Standard deviation | Glycemic variability :standard deviation [SD] | 6 month | 
| Number of mild hypoglycemia | Number of mild hypoglycaemia in two weeks | 6 month | 
| Number of severe hypoglycemia | Number of severe hypoglycemia in the last 6 months | 6 month | 
| Number of hyperglycemia | Number of hyperglycemia> 250 mg / dl in two weeks | 6 month | 
| Episodes of ketosis | Episodes of ketosis in the last 6 months | 6 month | 
| Number os hospital admissions | Number of hospital admissions for acute diabetes decompensation in the last 6 months. | 6 month | 
| Quality of life questionnaire in diabetes (DQOL) | 34 items on the quality of life of people with type 1 diabetes | 6 month | 
| Scale of adherence to treatment in patients with diabetes type 1 (DM1) | 15 items related to adherence to patient treatment | 6 month | 
| Diabetes distress scale. DDS | 17 items on the problems and stress that people with type 1 diabetes suffer (Polonski y col, 2005) | 6 month | 
| Fear of hypoglycemia: Questionnaire FH-15 | 15 items related to the fear of hypoglycemia in patients with type 1 diabetes | 6 month | 
| Diabetes treatment satisfaction questionnaire (DTSQ). | 8 items concerning the satisfaction of the treatment | 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxidation, Insulin analogues, Type 1 diabetes mellitus