Effect Pulsatile IV Insulin Therapy on the Quality of Life in Patients With Types 1 and 2 Diabetes

This study has been terminated.
(Administrative)
Sponsor:
Collaborator:
Advanced Diabetes Treatment Centers
Information provided by:
Florida Atlantic University
ClinicalTrials.gov Identifier:
NCT00228878
First received: September 27, 2005
Last updated: August 25, 2009
Last verified: August 2009

September 27, 2005
August 25, 2009
March 2003
January 2010   (final data collection date for primary outcome measure)
Researchers will assess whether pulsatile IV insulin therapy can successfully reverse the abnormal underlying metabolism in diabetic patients to the point of improving their quality of life. [ Time Frame: Patients will complete a quality of life questionnaire prior to the start of treatment and quarterly thereafter to objectively determine if the patients identify quality of life improvement ] [ Designated as safety issue: No ]
We will assess whether Metabolic Activation Therapy can successfully reverse the abnormal underlying metabolism in diabetic patients to the point of improving their quality of life.
Complete list of historical versions of study NCT00228878 on ClinicalTrials.gov Archive Site
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Effect Pulsatile IV Insulin Therapy on the Quality of Life in Patients With Types 1 and 2 Diabetes
Quality of Life With and Without Pulsatile IV Insulin Therapy in Diabetes.

The purpose of this study is to determine if restoring normal metabolic function in patients with either type I or type II diabetes can improve the impact of the consequences of diabetic complications on the overall quality of life of diabetic patients. Patients are treated once a week with pulsatile intravenous insulin therapy mimicking normal insulin secretion. A 44 item questionnaire is completed prior to the start of the treatment and quarterly thereafter with detailed analysis performed to measure progress and outcomes.

It is known that the glucose metabolic pathway (glycolysis) is the primary fuel generator in the brain and nerve tissue, the heart and vascular tissue, the eye, the kidney and the liver Deficient metabolic states such as seen in the glucose metabolism of diabetics can lead to sequelae. These damaging effects are exacerbated by altered cellular metabolites, specifically the increase in catabolic and decrease in anabolic factors. It has been shown over the past twenty years that normalization of metabolism in diabetic patients can be accomplished by mimicking the normal endogenous insulin pattern (ie., in pulses). Pulsatile insulin infusion has been demonstrated to reverse the diabetic metabolic state from primary fat utilization to carbohydrate utilization. This has been correlated with a stabilization of kidney function in patients with overt diabetic nephropathy, stabilization of blood glucoses, stabilization of blood pressure patterns, and reversal of hypoglycemic unawareness.

The Diabetes Impact Measurement Scale was originally developed to assess quality of life in patients with types 1 and 2 Diabetes Mellitus. This study measures whether the reversal of abnormal metabolism in patients with diabetes is correlated with an improvement in their quality of life.The respiratory quotient (RQ) is a measurement of CO2 exhaled and O2 inhaled and is proportionate to the fuel sources being used by the body, primarily the liver over short periods of time. The higher the RQ, the more glucose and less alternative fuel sources are being utilized. Following the RQ change helps determine the effectiveness of physiological insulin administration in increasing anabolic functions in diabetic individuals. By improving the body's glucose metabolism and thereby causing beneficial effects of anabolic factors, the possibility of serious complications can be decreased. In addition the use of oral carbohydrate at the same time along with the physiologic insulin administration stimulates the appropriate gut hormones which augment this effect, a response which cannot be duplicated with intravenous glucose. The purpose of our studies is to determine whether the physiologic administration of insulin along with the augmenting effect of oral carbohydrates will normalize metabolism in diabetic patients and improve their quality of life indices.

The RQ is determined by the use of a metabolic cart. Individuals breathe into a mask for 3-5 minutes after a rest period of 30 or more minutes. The ratio of exhaled volume of CO2 to the inhaled volume of O2 is determined as the RQ. The physiologic range is 0.7 to1.3. Individuals using fat as a primary fuel have a ratio of 0.7, protein or mixed fuels is 0.8-0.9 and carbohydrate is 0.9-1.0. Those taking excessive calories will have RQ's higher than 1.05. The RQ can be followed serially and this is done before and after each pulsatile IV insulin treatment, during the 3 successive sessions on a single treatment day. The amount of intravenous insulin and oral glucose given is determined by the RQ changes during the previous session.pulsatile IV insulin therapy encourages the glucose metabolism in diabetics to normalize in multiple organs, especially muscle, retina, liver, kidney and nerve endings. The process fundamentally requires the administration of high dose insulin pulses similar to those found in non diabetic humans by their pancreas into the surrounding portal circulation. Oral carbohydrates are given simultaneously to augment the process and prevent hypoglycemia. The process is monitored by frequent glucose levels and respiratory quotients (RQ). RQ is measured by a metabolic cart which determines the ratio VCO2/ VO2. This ratio is specific for the fuel used at any one time by the body. The glucose levels are monitored to keep glucose levels appropriate and the RQ determines the need to readjust the infusion protocol in each patient for subsequent insulin infusion sessions.Patient is evaluated post session and discharged when stable.

Frequent monitoring of RQ is necessary as these levels change rapidly, depending on the fuel being utilized by the body. Pulsatile IV insulin therapy shifts metabolism from primarily fatty acid metabolism to primarily glucose metabolism. This shift is reflected by the increase in respiratory quotient. However during rest periods the RQ may fall back to lower levels. Therefore RQ's are done at the beginning and at the end of each insulin infusion session of 1 hour in order to appropriately monitor and adjust insulin and carbohydrate loads to reach optimal activation in each session.

Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Diabetes Mellitus
Procedure: Effects of Pulsatile IV insulin on Diabetic Quality of Life
Patients receive weekly treatments of Pulsatile Intravenous insulin therapy. The patient's Endocrinologist determines the insulin dosage each week based upon the patient's response to treatment and their insulin resistance.
Other Name: Humulin, Humulog, Novolog
Active Comparator: 1
Diabetic patients will complete diabetic impact measurement scale questionnaires at baseline and quarterly thereafter in order to determine and track outcomes after the start of pulsatile intravenous insulin therapy.
Intervention: Procedure: Effects of Pulsatile IV insulin on Diabetic Quality of Life

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
500
June 2010
January 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • The researchers will include up to 200 patients both male and female between the ages of 21 and 85 diagnosed with type 1 or type 2 diabetes mellitus.
  • Self reporting or diagnosed with significant complications resulting from diabetes
  • Taking oral agents and/or insulin for diabetic control
  • Under an Endocrinologists supervision for their diabetes management. Endocrinologist must assess and approve patient for participation in this study
  • Ability to swallow without difficulty
  • Ability to commit to the weekly time requirements associated with the study

Exclusion Criteria:

  • Other causes of complications not related to diabetes
  • Inability to respond to 44 item questionnaire
  • Lack of intravenous access
  • Pregnancy
  • Alcohol abuse, drug addiction or the use of illegal drugs
  • Positive HIV
  • Inability to breathe into machine for respiratory quotients
Both
21 Years to 85 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00228878
H09-66-QOL
Yes
Betty Tuller PhD Professor of Complex Systems and Brain Sciences, Florida Atlantic University
Florida Atlantic University
Advanced Diabetes Treatment Centers
Principal Investigator: Betty Tuller, Ph.D Florida Atlantic University
Florida Atlantic University
August 2009

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