Diabetes MellitusPhase 3NCT01029444
Effects of Pulsed Intravenous (IV) Insulin on Brittle and Uncontrolled Diabetes
A Phase 3 study testing Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog ) in people with Diabetes Mellitus, run by Florida Atlantic University at 1 site in United States.
Trial summary
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 specifically on the wide swings in blood glucoses with erratic control even under optimal conditions. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Diabetes Mellitus
- What is being tested?
- Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog )
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Mar 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The researchers will include up to 300 patients both male and female between the ages of 18 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Florida Atlantic University
Boca Raton, Florida, 33421
About this study
Official title: Effects of Pulsatile Intravenous Insulin on Brittle Diabetes and Glucose Control
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 specifically on the wide swings in blood glucoses with erratic control even under optimal conditions. Patients are treated once a week with pulsatile intravenous insulin therapy mimicking normal insulin secretion. Blood sugar diaries and laboratory tests including quarterly Hemoglobin A1c levels are monitored to measure progress and outcomes.
Read the detailed description
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 (i.e., in pulses). Pulsatile intravenous insulin infusion has been demonstrated to stabilize the erratic wide swings in blood glucose levels and the overall stabilization of hyperglycemic and hypoglycemic events in Type 1 diabetic patients. This study was established to evaluate the effect of providing pulsatile intravenous insulin therapy on both type 1 and type 2 diabetes to determine the effect on improving diabetic control on patients with high blood glucose levels in spite of multiple insulin injections and wide swings in blood sugar despite good control.
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
- Conditions
- Diabetes Mellitus
- Being tested
- Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog )
- Keywords
- Diabetes, Pulsatile intravenous insulin, Oral carbohydrate loading, Respiratory Quotients, Hypoglycemia, Hyperglycemia, Diabetes Mellitus, with complications
- Medical subject headings
- Diabetes Mellitus, Hypoglycemia, Hyperglycemia, Diabetes Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog )Procedure or surgery
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 RQ levels and their insulin resistance.
| Study group | Role | What they receive |
|---|---|---|
| Insulin | Experimental | Brittle diabetic patients or patients with uncontrolled blood sugars will complete blood sugar diaries weekly and have hemoglobin A1c lab tests performed quarterly to evaluate progress in stabilizing blood sugars. Receives: Procedure: Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the effectiveness of Pulsed IV Insulin Therapy on the stabilization of blood glucose levels on patients with brittle or uncontrolled diabetes
Measured: Blood sugar diaries are collected weekly and HA1c labs are collected at baseline and quarterly to assess progress
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2009 (estimated)
- Study startMar 2007
- Primary completionMar 2011
- Study completionMar 2012
Why it stopped: Administrative
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Florida Atlantic University
- Sponsor type
- University, hospital or other
- Collaborators
- Advanced Diabetes Treatment Centers
- Investigators
- Betty Tuller, PhD, Study director, Florida Atlantic University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01029444
- Sponsor's protocol ID
- H09-66 BUD
- Status last verified
- Feb 2016
- First submitted
- 6 Aug 2009
- Last updated
- 3 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Pulsatile Intravenous Insulin on Brittle Diabetes and Glucose Control
- ClinicalTrials.gov ID
- NCT01029444
- Acronym / sponsor ID
- H09-66 BUD
- Conditions
- Diabetes Mellitus
- Keywords
- Diabetes, Pulsatile intravenous insulin, Oral carbohydrate loading, Respiratory Quotients, Hypoglycemia, Hyperglycemia, Diabetes Mellitus, with complications
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administrative
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Florida Atlantic UniversityUniversity, hospital or other
- Collaborators
- Advanced Diabetes Treatment Centers
- Study start
- Mar 2007
- Primary completion
- Mar 2011 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 10 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 specifically on the wide swings in blood glucoses with erratic control even under optimal conditions. Patients are treated once a week with pulsatile intravenous insulin therapy mimicking normal insulin secretion. Blood sugar diaries and laboratory tests including quarterly Hemoglobin A1c levels are monitored to measure progress and outcomes.
Detailed description
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 (i.e., in pulses). Pulsatile intravenous insulin infusion has been demonstrated to stabilize the erratic wide swings in blood glucose levels and the overall stabilization of hyperglycemic and hypoglycemic events in Type 1 diabetic patients. This study was established to evaluate the effect of providing pulsatile intravenous insulin therapy on both type 1 and type 2 diabetes to determine the effect on improving diabetic control on patients with high blood glucose levels in spite of multiple insulin injections and wide swings in blood sugar despite good control.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Insulin | Experimental | Procedure: Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog )Brittle diabetic patients or patients with uncontrolled blood sugars will complete blood sugar diaries weekly and have hemoglobin A1c lab tests performed quarterly to evaluate progress in stabilizing blood sugars. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The researchers will include up to 300 patients both male and female between the ages of 18 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog )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 RQ levels and their insulin resistance. | Procedure or surgery | Insulin |
Primary outcome
Evaluate the effectiveness of Pulsed IV Insulin Therapy on the stabilization of blood glucose levels on patients with brittle or uncontrolled diabetes
Time frame: Blood sugar diaries are collected weekly and HA1c labs are collected at baseline and quarterly to assess progress
Results and safety
The study was stopped early (reason given: Administrative). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Betty Tuller, PhD study director
Florida Atlantic University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pulsatile Intravenous Insulin Therapy (Humulin, Humulog, Novolog ) in people with Diabetes Mellitus, run by Florida Atlantic University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Administrative). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the effectiveness of Pulsed IV Insulin Therapy on the stabilization of blood glucose levels on patients with brittle or uncontrolled diabetes (time frame: Blood sugar diaries are collected weekly and HA1c labs are collected at baseline and quarterly to assess progress). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2016.