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Insulin Effects on Cardiac Function in Patients With Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02962921
Recruitment Status : Completed
First Posted : November 15, 2016
Last Update Posted : November 15, 2016
Sponsor:
Information provided by (Responsible Party):
Rambam Health Care Campus

Tracking Information
First Submitted Date  ICMJE September 10, 2016
First Posted Date  ICMJE November 15, 2016
Last Update Posted Date November 15, 2016
Study Start Date  ICMJE February 2003
Actual Primary Completion Date May 2003   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
Left ventricle ejection fraction (%) [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2016)
Time needed to exert insulin effect on myocardial function (hour) [ Time Frame: 1 year ]
Describe the shortest time required for insulin to change myocardial function.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 9, 2016)
  • Blood insulin levels (μU/ml: micro international unit per milliliter) [ Time Frame: 1 year ]
  • Left ventricle fractioning shortening (%) [ Time Frame: 1 year ]
  • E wave (centimeter per second) [ Time Frame: 1 year ]
  • A wave (centimeter per second) [ Time Frame: 1 year ]
  • E deceleration time (seconds) [ Time Frame: 1 year ]
  • E' (centimeters) [ Time Frame: 1 year ]
  • A' (centimeters) [ Time Frame: 1 year ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Insulin Effects on Cardiac Function in Patients With Diabetes Mellitus
Official Title  ICMJE Acute Insulin Effects on Cardiac Function in Patients With Diabetes Mellitus
Brief Summary

Our investigation studies the role of acute insulin administration on the diabetic heart, its corresponding effective blood-insulin level and the time-course applicability of insulin in a routine clinical setting.

A case series of six male (48.1 ± 4.9 y/o) patients with controlled diabetes (HbA1c of 6.6 ± 0.3%, disease duration of 14.4 ± 6.7 yr). Each subject was evaluated for glucose homeostatic, hemodynamic and echocardiographic systolic and diastolic parameters at baseline and following two successive insulin-load steps of a euglycemic hyperinsulinemic clamp study, each 2 h in duration. Results are presented as a mean ± SEM and analysed using the student's t-test.

Detailed Description

Patients:

Six male diabetic (five type 2 and one type 1) patients, 30-65 year old, with an established diagnosis of diabetes mellitus for ≥2 years, who were free of significant valvular heart disease, atrial arrhythmia or cardiac pacing comprised the study population. Patients' characteristics are summarized in table 1.

Each patient served as his or her own control. The study protocol was approved by the ethics committee at Rambam Medical Center, Haifa, Israel. Prior to the study, patients gave written informed consent after receiving a detailed explanation as to the purpose of the study, the technique, its side effects and the study protocol.

Patients were studied within a clinical research facility at the Rambam Medical Center, Haifa, Israel. Baseline evaluation was conducted at 8:00 am after 12 h of fasting, followed by two hyperinsulinemic euglycemic clamp (EHC) steps (2 h each step); The following vital signs were monitored during the study protocol: manual heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and baseline 12-lead electrocardiogram (ECG) recording. Glucose consumption rates against changing insulin levels were measured by the EHC technique. Cardiac function parameters were measured in the last 10 min of each step by tissue Doppler echocardiography. Results are presented as a mean ± SEM.

Clamp technique:

Each patient underwent an EHC study according to the protocol described previously, and implemented in our institute. Baseline measurements of blood insulin and glucose levels were collected. Thereafter, two insulin loads were initiated. The blood glucose level was kept near euglycemia (90 ± 5 mg/dl) throughout 2 h period of each insulin load step. Intravenous (iv) insulin loads were administered by 1- and 10-mU/kg·min at steps 1 and 2 of insulin loading (Lispro Insulin, Eli Lilly, France), respectively. Dexstrose in water 50% (DW50) was infused at variable infusion rates, titrated to maintain euglycemia. Concomitant saline 0.45% was used to dilute the DW50 in order to prevent hypertonicity-induced irritation of the cannuled vein. During the baseline period, saline 0.45% infusion rates were 0.75 ml/min to keep the iv cannule open. Every patient was given a chance to urinate before step 2.

Glucose and insulin homeostatic parameters of the study group were compared to those of healthy controls we studied earlier.

Cardiac function assessment:

Transthoracic echocardiography was performed by a qualified echocardiographer using a General Electric Vivid 3 machine (Tirat HaCarmel, Israel). Parameters were assessed as the mean of three consecutive heart beats.

Systolic echocardiographic parameters:

LV fractional shortening (LVFS) derived from end diastolic and end systolic LV dimensions; LV ejection fraction (LVEF) derived from end diastolic and end systolic LV volumes.

Diastolic echocardiographic parameters:

  1. Mitral valve diastolic flow parameters by pulse wave Doppler: E wave, represents early diastolic filling; A wave, represents late diastolic filling concomitant with the atrial kick, E/A ratio and E wave deceleration time (DT).
  2. Tissue Doppler-derived velocities of the mitral annulus: E' represents early diastolic velocity synchronous to the mitral inflow E wave, measured close to the interventricular septum (E' medial) and lateral wall (E' lateral); E' mean, derived from E' lateral and E' medial. A' represents late diastolic velocity to the synchronous mitral inflow A wave, measured close to the septum (A' medial) and lateral wall (A' lateral). A' mean is derived from A' lat. and A' med. A' reflects mitral annulus movement during atrial contraction. The E to E' ratio represents diastolic LV compliance.

Results are presented as mean ± SEM and analyzed using the student's t-test. Statistical significance considered when p value less than 0.05.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetes Mellitus
  • Ventricular Dysfunction
Intervention  ICMJE Drug: Insulin LISPRO intravenous loading
intravenous infusion of insulin Lispro.
Other Name: Humalog Insulin
Study Arms  ICMJE Experimental: Diabetic patients

Diabetic patients were treated with insulin loads, left ventricle functional parameters were compared to those of healthy persons.

Metabolic indices of insulin effect: blood insulin levels, glucose disposal rates under insulin infusion, were compared to respective group of healthy persons, studied earlier at our institution Insulin LISPRO intravenous loading

Intervention: Drug: Insulin LISPRO intravenous loading
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 9, 2016)
6
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 2004
Actual Primary Completion Date May 2003   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diabetes mellitus duration of 2 years and over.

Exclusion Criteria:

  • Previous cardiac disease: valvular, Pacing, Arrhythmias, Primary Cardiomyopathy.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 30 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02962921
Other Study ID Numbers  ICMJE 1558-RMB-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: First we need to learn how to share data
Responsible Party Rambam Health Care Campus
Study Sponsor  ICMJE Rambam Health Care Campus
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Eddy Karnieli, MD Professor emeritus, Faculty of medicine, Technion. Haifa, Israel
Principal Investigator: Ronen Bar Yoseph, MD Pediatric Pulmonary Institute
Principal Investigator: Sergey Yalonetsky, MD Cardiology Division
PRS Account Rambam Health Care Campus
Verification Date November 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP