Pulsatile Insulin Infusion Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 4

Summary: 
      This study is an open label, prospective, randomised comparative, single center study. In the
      present study, the impact of a 12-week pulsatile insulin infusion therapy (PIT) with Humulin
      R 100 from
    

Detailed description: 
      During the screening visit the patient will arrive at the study site and written informed
      consent will be obtained. Inclusion and exclusion criteria will be controlled and blood will
      be drawn for HbA1c and safety parameters. A point of care treatment (POCT) pregnancy test
      will be conducted in women of childbearing age. Patient demographics and history will be
      collected and a physical examination will be performed. The patient will complete a QoL, the
      continous glucose monitoring (CGM) sensor will be placed and trained, and the schedules for
      the subsequent treatment visits will be made. Also, the randomization (2 h vs 3 h) will be
      performed.

      During the initiation visit , a series of clinical assessments will be made to document the
      patient status with respect to secondary complications: sensory nerve perception thresholds
      (tuning fork and path tester), retinopathy (RetinaVue camera). An ECG will be conducted, and
      blood will be drawn for assessment of the efficacy parameters. Thereafter the pulsatile
      insulin infusion therapy (PIT) procedure will be initiated.

      For each PIT procedure: a venous catheter will be placed into one superficial vein at one
      arm, which will be connected to the insulin infusion pump and a glucose infusion pump via a
      three-way connector. Endothelial function will be measured by means of the Vendys 2 device
      (manufacturer: endothelix). The blood glucose will be tested by means of a POCT meter and the
      CGM, and the PIT procedure will be started (10 pulses of 3 U of regular human insulin per
      hour). Blood glucose will be tested every 5 to 10 min and glucose infusion will be started
      once a drop in blood glucose is detected. Adjustment of glucose administration will be
      performed until a stable glucose value between 80 mg/dL to 160 mg/dL is reached. In parallel,
      endothelial function will be measured every 30 min. At the end of the PIT procedure, the
      venous catheter will be removed and the patient will be discharged until the next visit.

      During all consecutive treatment visits the patient will arrive at the investigational site
      at the agreed time-point and information regarding potential adverse events will be
      collected. Vital signs will be measured and the PIT procedure will be performed as described.
      At visits V6 and V10 additional examinations (assessments of neuropathy and retinopathy,
      blood draws for efficacy parameters, diabetes treatment satifaction questionnaire (DTSQ)
      questionnaire) will be performed.

      During the final Visit the assessments from baseline (ECG, physical examination, neuropathy
      assessments, retinopathy assessment, blood draws for all safety and efficacy parameters incl.
      messenger ribonucleic acid (mRNA) analysis) will be repeated. The patient will complete a
      final DTSQ questionnaire, which concludes the participation in the trial.
    

Intervention name(s): 3 hours humulin R 100 IU/mL PIT; 2 hours humulin R 100 IU/mL PIT
Intervention type(s): Drug; Drug
Intervention description(s): PIT procedure: a venous catheter will be placed into one superficial vein at one arm, which will be connected to the insulin infusion pump and a glucose infusion pump via a three-way connector. Endothelial function will be measured by means of the Vendys 2 device. The blood glucose will be tested by means of a POCT meter and the CGM, and the PIT procedure will be started (10 pulses of 3 U of regular human insulin per hour). Blood glucose will be tested every 5 to 10 min and glucose infusion will be started once a drop in blood glucose is detected. Adjustment of glucose administration will be performed until a stable glucose value between 80 mg/dL to 160 mg/dL is reached. In parallel, endothelial function will be measured every 30 min. At the end of the PIT procedure, the venous catheter will be removed and the patient will be discharged until the next visit.; As described for the Intervention "3 hours of pulsatile insulin infusion (PIT) with humulin R 100 IU/mL", the treatment duration is just one hour less.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin, Isophane
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 1 arm of 2 hours pulsatile insulin infusion treatment vs. a second arm of 3 hours pulsatile insulin infusion treatment.
Masking: None (Open Label)
Primary purpose: Treatment