We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 8 of 28 for:    Recruiting, Not yet recruiting, Available Studies | "Type 1 Diabetes" | NIDDK

Glucose Counterregulation in Long Standing Type 1 Diabetes

This study is currently recruiting participants.
Verified February 2017 by University of Pennsylvania
Sponsor:
ClinicalTrials.gov Identifier:
NCT01474889
First Posted: November 18, 2011
Last Update Posted: February 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Pennsylvania
  Purpose

The Investigator is in the final phase of this study and is searching for a Hypo-AWARE Type 1 diabetic control group (Group 2). The primary goal for Group 2 in this study; is to demonstrate how hormones of Type 1 diabetics should react during hypoglycemic and non-hypoglycemic events.

Enrollment for Group 1 (Hypo-Unaware) and Group 3 (Non-diabetic) is complete.

This study is designed to determine if real-time continuous glucose monitor (RT-CGM) can reverse defective Glucose counter regulation and hypoglycemia unawareness in long standing type 1 diabetes.


Condition Intervention
Hypoglycemia Unawareness Type 1 Diabetes Healthy Device: RT-CGM

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effect of Real-Time Continuous Glucose Monitoring on Glucose Counterregulation in Long Standing Type 1 Diabetes

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Endogenous glucose production [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • Endogenous Glucose Production [ Time Frame: 18 months ]
  • Magnitude and Glycemic thresholds for counter-regulatory Hormonal and Symptom Responses [ Time Frame: 6 months ]
  • Magnitude and Glycemic thresholds for counter-regulatory Hormonal and Symptom Responses [ Time Frame: 18 months ]

Estimated Enrollment: 36
Study Start Date: October 2011
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Hypoglycemia Unaware T1 Diabetes RT-CGM
Type 1 Diabetes with Hypoglycemia Unawareness. Patients wear an RT-CGM for 18 months. We are comparing type 1 diabetic patients who experience severe hypoglycemia unawareness to two other (control) groups: Type 1 diabetic patients without hypoglycemia unawareness and patients who are not diabetic at all. The control groups will only have 3 visits. We plan to study glucose production and symptom generation during insulin-induced hypoglycemia (metabolic testing) by subjecting each group to a pair of metabolic clamps (hypoglycemic and euglycemic) at baseline. This group of Hypoglycemia unaware diabetics will have an additional two sets of clamps at 6 months and 18 months after wearing the RT-CGM to determine if hypoglycemia avoidance can reverse unawareness.
Device: RT-CGM
Each device is approximately the size of a pager and transmits with a subcutaneously placed sensor consisting of a 21 - 26 gauge needle 5 - 12 mm in length. Sensors are placed using sterile precautions and changed every 3 - 7 days depending on the manufacturers' instructions. All devices are approved as adjunctive tools to blood glucose monitoring that will be continued at least 4 times daily, before each meal and at bedtime.
Other Name: DexCom SEVEN PLUS, Guardian R-T, or FreeStyle Navigator.

Detailed Description:

The present protocol is designed to determine whether strict hypoglycemia avoidance by real-time continuous glucose monitoring (RT-CGM), can restore endogenous glucose production in response to hypoglycemia in patients with long standing disease. Twelve subjects with long standing type 1 diabetes complicated by hypoglycemia unawareness underwent assessment of the endogenous glucose production response to insulin-induced hypoglycemia using paired hyperinsulinemic eu- and hypoglycemic clamps with stable glucose isotope infusions before and at 6 and 18 months following initiation of RT-CGM. The primary analysis will be change in the endogenous glucose production response from before to 6 months following initiation of RT-CGM, and a secondary analysis will consider the persistence of any change at 18 months. The clinical significance of any determined changes in the endogenous glucose production response to insulin-induced hypoglycemia will be determined by comparison to responses obtained using paired hyperinsulinemic eu- and hypoglycemic clamps on one occasion in a matched control group of 12 subjects with long-standing type 1 diabetes but no hypoglycemia unawareness (GROUP 2) and in a matched control group of 12 nondiabetic subjects (GROUP 3). The Investigator is now ONLY recruiting for GROUP 2.

Enrollment for Group 1 (Hypo-Unaware) and Group 3 (Non-diabetic) is complete.

Hypoglycemia is a major barrier to the achievement of adequate glycemic control for most patients with insulin-dependent diabetes. Type 1 diabetic patients with absolute insulin deficiency (C-peptide negative) are at greatest risk for experiencing severe hypoglycemic events because the near total destruction of insulin producing islet β-cells produces an associated defect in glucagon secretion from neighboring α-cells. Such patients then depend on the sympathoadrenal system as a final defense against hypoglycemia, but unfortunately, recurrent episodes of hypoglycemia blunt sympathoadrenal activation and produce a syndrome of hypoglycemia unawareness that is associated with a twenty-fold increased risk of life-threatening hypoglycemia. Without intact islet or sympathoadrenal (especially epinephrine) responses to hypoglycemia, these patients cannot increase endogenous (primarily hepatic) glucose production to prevent or correct low blood glucose.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   25 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria for GROUP 2 only (Group 1 and Group 3 are complete)

  1. Male and female subjects age 25 to 70 years.
  2. Able to provide written informed consent and to comply with the procedures of the study protocol.
  3. Clinical history compatible with type 1 diabetes with disease onset < 40 years of age
  4. Insulin-dependent for > 10 years
  5. Absent C-peptide (< 0.3 ng/mL).
  6. Involvement in intensive diabetes management defined as the use of basal-bolus insulin analog delivery by multi-dose injection (MDI) or continuous subcutaneous insulin infusion (CSII) together with self-monitoring of blood glucose values four or more times daily, without continuous glucose monitoring (CGM), under the direction of an endocrinologist, diabetologist, or diabetes nurse practitioner with at least 3 clinical evaluations during the previous 12 months.
  7. Intact hypoglycemia awareness indicated by a Clarke score of 3 or less. 8. No episodes of severe hypoglycemia in the past 3 years.

Key Exclusion Criteria for all 3 groups

  1. Body mass index (BMI) greater than 30 kg/m2.
  2. Insulin requirement of more than 1.0 IU/kg/day.
  3. HbA1c greater than 10%.
  4. Untreated proliferative diabetic retinopathy.
  5. SBP greater than 160 mmHg or DBP greater than 100 mmHg.
  6. Glomerular filtration rate (GFR) less than 55 ml/min/1.73 m-squared
  7. Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study.
  8. Baseline hemoglobin less than 11 g/dl in women and less than12 g/dl in men.
  9. Severe co-existing cardiac disease
  10. Persistent elevation of liver function tests greater than 1.5 upper normal limits
  11. Hyperlipidemia despite medical therapy
  12. Receiving treatment for a medical condition requiring chronic use of systemic steroids
  13. Presence of a seizure disorder not attributable to hypoglycemia.
  14. Untreated hypothyroidism, Addisons disease, or Celiac disease.
  15. Treatment with any anti-diabetic medication other than insulin within 4 weeks of enrollment.
  16. Use of RT-CGM (continuous glucose monitor) within last 4 weeks.

    • Non-diabetic patients do not need to meet any of the glucose criteria.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01474889


Contacts
Contact: (Ginger) Cornelia V. Dalton- Bakes, CRC 215 746 2085 cornelia.dalton-bakes@uphs.upenn.edu
Contact: Amy Peleckis, NP 215 746 2084 amy.peleckis@uphs.upenn.edu

Locations
United States, Pennsylvania
Clinical and Translational Research Center, Hospital of University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ginger (Cornelia V) Dalton-Bakes    215-746-2085    cornelia.dalton-bakes@uphs.upenn.edu   
Contact: Amy Peleckis    215-746-2084    amy.peleckis@uphs.upenn.edu   
Principal Investigator: Michael R Rickels, M.D., M.S.         
Rodebaugh Diabetes Center, University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ginger (Cornelia V) Bakes    215-746-2085    cornelia.dalton-bakes@uphs.upenn.edu   
Contact: Amy Peleckis    215-746-2084    amy.peleckis@uphs.upenn.edu   
Principal Investigator: Michael R. Rickels, M.D., M.S.         
Sub-Investigator: Mark H. Schutta, M.D.         
University of Pennsylvania - Institute for Diabetes, Obesity and Metabolism Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ginger (Cornelia V) Bakes, CRC    215-746-2085    cornelia.dalton-bakes@uphs.upenn.edu   
Contact: Amy Peleckis, NP    215 746-2084    amy.peleckis@uphs.upenn.edu   
Principal Investigator: Michael R Rickels, MD., MS         
Sponsors and Collaborators
University of Pennsylvania
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Michael R Rickels, M.D., M.S. University of Pennsylvania
  More Information

Publications:
Hermanides J, Norgaard K, Bruttomesso D, Mathieu C, Frid A, Dayan CM, Diem P, Fermon C, Wentholt IME, Hoekstra JBL, DeVries JH: Sensor augmented pump therapy substantially lowers HbA(1c); a randomized controlled trial. Diabetologia 52:S43, 2009

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01474889     History of Changes
Other Study ID Numbers: 814114
R01DK091331-01 ( U.S. NIH Grant/Contract )
First Submitted: November 15, 2011
First Posted: November 18, 2011
Last Update Posted: February 28, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by University of Pennsylvania:
Hypoglycemia, Unawareness, RT-CGM, Type 1 Diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Hypoglycemia
Unconsciousness
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms