Clinical trial NCT02914886: Beneficial Effect of Insulin Glulisine by Lipoatrophy and Type 1 Diabetes (LAS)
Official title: Lipoatrophy in Children, Adolescents and Adults With Modern Treatment Modalities: is There a Beneficial Effect of Insulin Glulisine?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes
Lipoatrophy
Keywords: Diabetes
Lipoatrophy
children
adolescents
adults
insulin therapy
Lead sponsor: Kinderkrankenhaus auf der Bult
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2016-09-26
Enrollment: 14
Sex: ALL
Minimum age (years): 6
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate whether a zinc-free insulin is an effective treatment option for lipoatrophy in patients with type 1 Diabetes (T1D) and insulin pump (CSII, continuous subcutaneous insulin infusion) therapy.

Detailed description: Randomized, controlled, open-label parallel study. Clinical Study Phase IV After being included in the study, subjects are getting an extensive dermatological examination by a pediatric dermatologist familiar with cutaneous complications of T1D, additionally pathological results will be documented by photography and, if necessary, videodermoscopy. Additionally, an evaluation of their lipoatrophic areas using imaging methods like ultrasound (USG) and MRI will be performed. After randomization, half of the included children switch their pump insulin into insulin glulisine (intervention group) for 6 months. The others continue their current treatment (control group) and switch to insulin glulisine 6 months later. Both groups are followed-up until month 12. Hence, after the 4th visit at 6 months, all enrolled patients are on insulin glulisine pumps for a further period of 6 months.

Eligibility criteria: Inclusion Criteria:

* Patients with type 1 diabetes and documented lipoatrophy at injection sites on CSII treatment
* Age between 6 and 40 years (both inclusive, see rationale for the inclusion of minors above)
* Signed informed consent form from patients or from parents/their guardians if children/youths \<18 years
* Patients must be willing to undergo all study procedures

Exclusion Criteria:

* Patients with previous use of insulin glulisine
* Patients requiring corticosteroids as treatment medication. NOTE inhaled corticosteroids are allowed.
* Patients suffering from severe chronic disease other than T1D or genetic disorder (i.e. Down syndrome etc.)
* Pregnant or lactating women
* Patients participating in other device or drug studies
* History of drug or alcohol abuse within the last five years prior to screening
* Anamnestic history of hypersensitivity to the study drugs (or any component of the study drug) or to drugs with similar chemical structures
* History of severe or multiple allergies
* Treatment with any other investigational drug within 3 months prior to screening
* Progressive fatal disease
* History of significant cardiovascular (such as myocardial infarction, stroke, TIA), respiratory, gastrointestinal, hepatic (ALT and/or AST \> 3 times the normal reference range), renal (creatinine \> 1.1 mg/dl in women and \> 1.5 mg/dl in men), neurological, psychiatric and/or hematological disease as judged by the investigator
* Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner
* Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
* Prisoners or subjects who are involuntarily incarcerated

Target Disease Exclusions

* History of T2DM, maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
* Any use of oral hypoglycemic agents within 12 months prior to the screening visit
* History of diabetes ketoacidosis (DKA) within 12 weeks prior to the screening visit
* History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 3 months prior to the screening visit
* Frequent episodes of hypoglycemia as defined by more than one episode requiring assistance, emergency care (paramedics or emergency room care) or glucagon therapy, or more than 2 unexplained episodes of symptomatic hypoglycemia within 3 months prior to the screening visit. An unexplained event is defined as an event that cannot be explained by circumstances such as dietary (e.g. missed meal), strenuous exercise, error in insulin dosing, etc.
* Hypoglycemic unawareness
* History of diabetes insipidus
* History of Addison's disease or chronic adrenal insufficiency

Physical and Laboratory Test Findings

* BMI above 35 kg/m2
* RR \> 180/110 mm Hg
* Aspartate aminotransferase (AST) \> 3X Upper limit of normal (ULN)
* Alanine aminotransferase (ALT) \> 3X ULN
* Serum total bilirubin \> 3X ULN
* Estimated GFR (eGFR) \< 60 ml/min/1.73 m2
* Hemoglobin ≤ 11.0 g/dl (110 g/l) for boys / men; hemoglobin ≤10.0 g/dl (100 g/L) for girls / women.
* Creatine kinase (CK) \> 3X ULN
* Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody.
* Abnormal Free T4 Note: abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded. A one-time retest may be allowed, as determined by the Investigator, after a minimum of 6 weeks following the adjustment of thyroid hormone replacement therapy in subject who have had a prior diagnosis of a thyroid disorder and who are currently receiving thyroid replacement therapy. Such cases should be discussed with the Investigator prior to retesting.

Primary outcomes:
measure: Relative thickness as assessed by MRI
timeFrame: at 6 months
Secondary outcomes:
measure: Relative thickness as assessed by MRI
timeFrame: at 6 and 12 months
measure: Relative thickness as assessed by MRI
timeFrame: at baseline and 12 months
measure: Relative thickness as assessed by USG
timeFrame: at 6 months
measure: Relative thickness as assessed by USG
timeFrame: at 6 and 12 months
measure: Relative thickness as assessed by USG
timeFrame: at baseline and 12 months
measure: indicator dermatoses of Diabetes mellitus and associated autoimmune disorders of the skin
timeFrame: at 6 and 12 months
measure: Number of new lipoatrophic areas
timeFrame: at 6 and 12 months
measure: Glycemic control
timeFrame: at 6 and 12 months
measure: Insulin requirements
timeFrame: at 6 and 12 months
measure: Laboratory findings
timeFrame: at baseline, 6 months and 12 months
measure: Side effects
timeFrame: within 12 months
Other outcomes:
Locations:
Study officials:
affiliation: Kinder- und Jugendkrankenhaus AUF DER BULT
name: Olga Kordonouri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kordonouri O, Biester T, Weidemann J, Ott H, Remus K, Grothaus J, Pisarek N, Hartmann R, Adolph K, Lange K, Danne T. Lipoatrophy in children, adolescents and adults with insulin pump treatment: Is there a beneficial effect of insulin glulisine? Pediatr Diabetes. 2020 Nov;21(7):1285-1291. doi: 10.1111/pedi.13094. Epub 2020 Aug 19.