Pulsatile Insulin Infusion Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus
Primary Purpose
Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
3 hours humulin R 100 IU/mL PIT
2 hours humulin R 100 IU/mL PIT
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2
Eligibility Criteria
Inclusion Criteria:
- Informed consent obtained prior to any trial-related activities
- Male or female > 18 years
- Diagnosed with Type 1 or 2 Diabetes ≥ 2 years
- HbA1c <10%
- Nephropathy with GFR between 30 and 60 mL/min/1,73m2 or < 75 GFR together with proteinuria and/or elevated creatinine levels
- Patient is naïve to pulsatile insulin treatment
Exclusion Criteria:
- Patients participating in another investigational drug study
- Current or history of dialysis therapy
- Anemia with hemoglobin < 10 g/dL
- Unstable significant cardiovascular disease with admission to emergency room or hospital in last 45 days
- Patients with diagnosed renal failure from non-diabetic etiology
- Pregnancy or breast feeding
- Patient unwillingness to use a CGM device, or inability (with or without family assistance) to replace the sensor every two weeks on the study CGM device
- Drug or alcohol abuse
- Sexually active woman of childbearing age not practicing birth control by accepted methods
- Lack of compliance or other reason that in the discretion of the investigator precludes satisfactory participation in the study
- Any severe illness preventing participation in the study per protocol (in the discretion of the investigator)
Sites / Locations
- NYC Research, Inc.
- Pfützner Science & Health Institute GmbH
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
3 hour pulsatile normal insulin infusion treatment
2 hour pulsatile normal insulin infusion treatment
Arm Description
the pulsatile insulin infusion treatment will be applied for 3 hours once a week with 10 pulses of 3 U of humulin R 100 IU/mL insulin per hour
the pulsatile insulin infusion treatment will be applied for 2 hours once a week with 10 pulses of 3 U of humulin R 100 IU/mL insulin per hour
Outcomes
Primary Outcome Measures
Endothelial function
Impact of PIT on endothelial function before and one hour after the PIT initiation measured with the Vendys2 device
Secondary Outcome Measures
Renal function
It will be assessed whether insulin resistance has improved or worsened over the course of the study.
Measured laboratory parameters for renal function (GFR, creatinine, proteinurea)
nerve function
Sensory nerve function (pathtester, tuning fork). It will be assessed whether insulin resistance has improved or worsened over the course of the study.
Retinopathy
Retinopathy will be measured with the RetinaVue device. It will be assessed whether Retinopathy has improved or worsened over the course of the study.
HbA1c
metabolic control
Insulin resistance
For assessment of insulin resistance glucose, retinol-binding protein 4 (RBP4), angiopoetin2, adiponectin, interleukin 6 (IL-6), hsCRP, glucagon, insulin, c-peptide, and intact Proinsulin will be measured. Finally, it is assessed whether insulin resistance has improved or worsened over the course of the study.
Diabetes treatment satisfaction questionnaire
Eight questions about the patient´s satisfaction with the diabetes treatment. Answer possibilities range form 1 (very good) to 10 (very bad)
Full Information
NCT ID
NCT04030091
First Posted
July 15, 2019
Last Updated
March 30, 2021
Sponsor
Sciema UG
Collaborators
Innovative Diabetes Treatment Studies LLC.
1. Study Identification
Unique Protocol Identification Number
NCT04030091
Brief Title
Pulsatile Insulin Infusion Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus
Official Title
Pilot Study for Evaluation of the Impact of Pulsatile Insulin Infusion Therapy on Vascular Function in Patients With Type 1 and Type 2 Diabetes Mellitus
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
September 6, 2019 (Actual)
Primary Completion Date
October 19, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sciema UG
Collaborators
Innovative Diabetes Treatment Studies LLC.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2, Diabetes Mellitus, Type 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
3 hour pulsatile normal insulin infusion treatment
Arm Type
Experimental
Arm Description
the pulsatile insulin infusion treatment will be applied for 3 hours once a week with 10 pulses of 3 U of humulin R 100 IU/mL insulin per hour
Arm Title
2 hour pulsatile normal insulin infusion treatment
Arm Type
Experimental
Arm Description
the pulsatile insulin infusion treatment will be applied for 2 hours once a week with 10 pulses of 3 U of humulin R 100 IU/mL insulin per hour
Intervention Type
Drug
Intervention Name(s)
3 hours humulin R 100 IU/mL PIT
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
2 hours humulin R 100 IU/mL PIT
Intervention Description
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.
Primary Outcome Measure Information:
Title
Endothelial function
Description
Impact of PIT on endothelial function before and one hour after the PIT initiation measured with the Vendys2 device
Time Frame
1 hour
Secondary Outcome Measure Information:
Title
Renal function
Description
It will be assessed whether insulin resistance has improved or worsened over the course of the study.
Measured laboratory parameters for renal function (GFR, creatinine, proteinurea)
Time Frame
13 weeks
Title
nerve function
Description
Sensory nerve function (pathtester, tuning fork). It will be assessed whether insulin resistance has improved or worsened over the course of the study.
Time Frame
13 weeks
Title
Retinopathy
Description
Retinopathy will be measured with the RetinaVue device. It will be assessed whether Retinopathy has improved or worsened over the course of the study.
Time Frame
13 weeks
Title
HbA1c
Description
metabolic control
Time Frame
13 weeks
Title
Insulin resistance
Description
For assessment of insulin resistance glucose, retinol-binding protein 4 (RBP4), angiopoetin2, adiponectin, interleukin 6 (IL-6), hsCRP, glucagon, insulin, c-peptide, and intact Proinsulin will be measured. Finally, it is assessed whether insulin resistance has improved or worsened over the course of the study.
Time Frame
13 weeks
Title
Diabetes treatment satisfaction questionnaire
Description
Eight questions about the patient´s satisfaction with the diabetes treatment. Answer possibilities range form 1 (very good) to 10 (very bad)
Time Frame
13 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Informed consent obtained prior to any trial-related activities
Male or female > 18 years
Diagnosed with Type 1 or 2 Diabetes ≥ 2 years
HbA1c <10%
Nephropathy with GFR between 30 and 60 mL/min/1,73m2 or < 75 GFR together with proteinuria and/or elevated creatinine levels
Patient is naïve to pulsatile insulin treatment
Exclusion Criteria:
Patients participating in another investigational drug study
Current or history of dialysis therapy
Anemia with hemoglobin < 10 g/dL
Unstable significant cardiovascular disease with admission to emergency room or hospital in last 45 days
Patients with diagnosed renal failure from non-diabetic etiology
Pregnancy or breast feeding
Patient unwillingness to use a CGM device, or inability (with or without family assistance) to replace the sensor every two weeks on the study CGM device
Drug or alcohol abuse
Sexually active woman of childbearing age not practicing birth control by accepted methods
Lack of compliance or other reason that in the discretion of the investigator precludes satisfactory participation in the study
Any severe illness preventing participation in the study per protocol (in the discretion of the investigator)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas Pfuetzner, Prof. Dr. Dr.
Organizational Affiliation
Pfützner Science & Health Institute GmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
NYC Research, Inc.
City
New York
State/Province
New York
ZIP/Postal Code
10455
Country
United States
Facility Name
Pfützner Science & Health Institute GmbH
City
Mainz
State/Province
Rhineland-Palatinate
ZIP/Postal Code
55128
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Pulsatile Insulin Infusion Therapy in Patients With Type 1 and Type 2 Diabetes Mellitus
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