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Effects of Pulsatile Insulin Delivery on Diabetic Neuropathy in Patients With Types 1 and 2 Diabetes Mellitus

Primary Purpose

Diabetes Mellitus, With Complications

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Effect of Pulsatile IV insulin on diabetic neuropathy
Effect of Pulsatile IV Insulin on diabetic neuropathy
Sponsored by
Florida Atlantic University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, With Complications focused on measuring Pulsatile intravenous insulin, Oral carbohydrate loading, Respiratory Quotients, Hypoglycemia, Diabetic Neuropathy

Eligibility Criteria

20 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The researchers will include up to 500 patients both male and female between the ages of 20 and 90 diagnosed with type 1 or type 2 diabetes mellitus. All patients were diagnosed by their endocrinologists as having diabetic neuropathy All patients had failed conventional treatment for diabetic neuropathy 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 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

Sites / Locations

  • Florida Atlantic University Center for Complex Systems and Brain Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

2

1

Arm Description

Patients with diagnosed diabetic neuropathy will receive objective baseline testing and follow up testing every six months after the start of Pulsatile intravenous insulin therapy to monitor and assess diabetic neuropathy.

Control patients with diabetic neuropathy will receive objective testing at baseline and every six months to compare and measure results with patients who are receiving pulsatile intravenous insulin therapy.

Outcomes

Primary Outcome Measures

Measure the stabilization or reduction of the decline of diabetic neuropathy by pt questionnaires and diagnostic tests

Secondary Outcome Measures

Full Information

First Posted
September 27, 2005
Last Updated
August 8, 2016
Sponsor
Florida Atlantic University
Collaborators
Advanced Diabetes Treatment Centers, Global Infusions
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1. Study Identification

Unique Protocol Identification Number
NCT00228891
Brief Title
Effects of Pulsatile Insulin Delivery on Diabetic Neuropathy in Patients With Types 1 and 2 Diabetes Mellitus
Official Title
Effects of Pulsatile Insulin Delivery on Peripheral Diabetic Neuropathy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Terminated
Why Stopped
Administrative
Study Start Date
February 2004 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Florida Atlantic University
Collaborators
Advanced Diabetes Treatment Centers, Global Infusions

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Diabetic neuropathy is a progressive complication causing serious problems in 25-40% of diabetic patients. Anecdotal reports have indicated improvement with pulsatile IV insulin in patients otherwise resistant to all conventional therapies. Significant complications produce painful peripheral dysesthesias, loss of sensation and gastroparesis. This study is designed to test the effectiveness of pulsatile insulin delivery on diabetic neuropathy.
Detailed Description
Diabetic neuropathy (DN) is a progressive complication causing serious problems in 25%-40% of diabetic patients. Significant complications produce painful peripheral dysesthesias, loss of sensation, and gastroparesis. DN may affect the peripheral motor and sensory nerves in addition to the autonomic nervous system (1-3). Treatment strategies for patients with DN have generally concentrated on pain relief, without addressing the underlying pathophysiology of the disease (4). Anecdotal reports from patients treated with pulsatile insulin for other complications suggest that this treatment may show efficacy in patients with DN. This study is designed to compare patients with DN who receive pulsatile insulin with a control group. Pulses of IV insulin 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 measuring of 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. The insulin pulses are delivered over 1-hour periods with a 1-hour rest period between each session. Three treatments are given during each treatment day. 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 correlate with an improvement in their manifestations of diabetic neuropathy. 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. Tesfaye S, Chaturvedi N, Eaton SEM, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH, Vascular Risk factors and Diabetic Neuropathy N Engl J Med 352:341-50, 2005. Neuropathy Trust, Diabetic Neuropathy:Prevalence, www.neurocentre.com. Potter PJ, Maryniak O, Yamorski R, Jones IC, Incidence of Peripheral Neuropathy in the Contralateral Limb of Persons with Unilateral Amputation due to Diabetes, Journal of Rehabilitation Research and Development 35:335-39, 1998. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengan , Duloxetine versus Placebo in Patients with Painful Diabetic Neuropathy, Pain 116:109-18, 2005.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, With Complications
Keywords
Pulsatile intravenous insulin, Oral carbohydrate loading, Respiratory Quotients, Hypoglycemia, Diabetic Neuropathy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Non-Randomized
Enrollment
152 (Actual)

8. Arms, Groups, and Interventions

Arm Title
2
Arm Type
Active Comparator
Arm Description
Patients with diagnosed diabetic neuropathy will receive objective baseline testing and follow up testing every six months after the start of Pulsatile intravenous insulin therapy to monitor and assess diabetic neuropathy.
Arm Title
1
Arm Type
Placebo Comparator
Arm Description
Control patients with diabetic neuropathy will receive objective testing at baseline and every six months to compare and measure results with patients who are receiving pulsatile intravenous insulin therapy.
Intervention Type
Procedure
Intervention Name(s)
Effect of Pulsatile IV insulin on diabetic neuropathy
Intervention Description
Control patients with diagnosed diabetic neuropathy will have objective testing at baseline and every six months to compare and measure results to patients receiving pulsatile intravenous insulin therapy.
Intervention Type
Procedure
Intervention Name(s)
Effect of Pulsatile IV Insulin on diabetic neuropathy
Other Intervention Name(s)
Humulog, Humulin, Novolog,
Intervention Description
Patients diagnosed with diabetic neuropathy will be treated with pulsatile intravenous insulin on a weekly basis. Patient's Endocrinologist will determine the dosage of intravenous insulin to be given each week based upon the patient's response and insulin resistance.
Primary Outcome Measure Information:
Title
Measure the stabilization or reduction of the decline of diabetic neuropathy by pt questionnaires and diagnostic tests
Time Frame
Measure the stabilization and reduction of complications associated with diabetic neuropathy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: The researchers will include up to 500 patients both male and female between the ages of 20 and 90 diagnosed with type 1 or type 2 diabetes mellitus. All patients were diagnosed by their endocrinologists as having diabetic neuropathy All patients had failed conventional treatment for diabetic neuropathy 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Betty Tuller, PhD
Organizational Affiliation
Florida Atlantic University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Florida Atlantic University Center for Complex Systems and Brain Sciences
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33431
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16108870
Citation
Gill G, Moulik P. Mortality and diabetic neuropathy. Diabet Med. 2005 Sep;22(9):1289. doi: 10.1111/j.1464-5491.2005.01729.x. No abstract available.
Results Reference
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PubMed Identifier
16150538
Citation
Moghtaderi A, Bakhshipour A, Rashidi H. Validation of Michigan neuropathy screening instrument for diabetic peripheral neuropathy. Clin Neurol Neurosurg. 2006 Jul;108(5):477-81. doi: 10.1016/j.clineuro.2005.08.003. Epub 2005 Sep 16.
Results Reference
background
PubMed Identifier
15673800
Citation
Tesfaye S, Chaturvedi N, Eaton SE, Ward JD, Manes C, Ionescu-Tirgoviste C, Witte DR, Fuller JH; EURODIAB Prospective Complications Study Group. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005 Jan 27;352(4):341-50. doi: 10.1056/NEJMoa032782.
Results Reference
background
PubMed Identifier
9704317
Citation
Potter PJ, Maryniak O, Yaworski R, Jones IC. Incidence of peripheral neuropathy in the contralateral limb of persons with unilateral amputation due to diabetes. J Rehabil Res Dev. 1998 Jul;35(3):335-9.
Results Reference
background
PubMed Identifier
15927394
Citation
Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain. 2005 Jul;116(1-2):109-18. doi: 10.1016/j.pain.2005.03.029.
Results Reference
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Effects of Pulsatile Insulin Delivery on Diabetic Neuropathy in Patients With Types 1 and 2 Diabetes Mellitus

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