Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Restoration of Hypoglycemia Awareness With Metoclopramide

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.
 
ClinicalTrials.gov Identifier: NCT03970720
Recruitment Status : Recruiting
First Posted : May 31, 2019
Last Update Posted : May 31, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Simon Fisher, University of Utah

Tracking Information
First Submitted Date  ICMJE May 29, 2019
First Posted Date  ICMJE May 31, 2019
Last Update Posted Date May 31, 2019
Actual Study Start Date  ICMJE May 28, 2019
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Change in Blood Glucagon [ Time Frame: 4 weeks ]
    Blood samples will be drawn from study participants during the initial hypoglycemic clamp study (Day 0) and during the second hypoglycemic clamp study (Day 28) following the 4-week intervention period. The average change in blood glucagon level will be compared between the study arms.
  • Change in Blood Epinephrine [ Time Frame: 4 weeks ]
    Blood samples will be drawn from study participants during the initial hypoglycemic clamp study (Day 0) and during the second hypoglycemic clamp study (Day 28) following the 4-week intervention period. The average change in blood epinephrine level will be compared between the study arms.
  • Change in Blood Norepinephrine [ Time Frame: 4 weeks ]
    Blood samples will be drawn from study participants during the initial hypoglycemic clamp study (Day 0) and during the second hypoglycemic clamp study (Day 28) following the 4-week intervention period. The average change in blood norepinephrine level will be compared between the study arms.
  • Change in Blood Cortisol [ Time Frame: 4 weeks ]
    Blood samples will be drawn from study participants during the initial hypoglycemic clamp study (Day 0) and during the second hypoglycemic clamp study (Day 28) following the 4-week intervention period. The average change in blood cortisol level will be compared between the study arms.
  • Change in Blood Pancreatic Polypeptide [ Time Frame: 4 weeks ]
    Blood samples will be drawn from study participants during the initial hypoglycemic clamp study (Day 0) and during the second hypoglycemic clamp study (Day 28) following the 4-week intervention period. The average change in blood pancreatic polypeptide level will be compared between the study arms.
  • Change in Hypoglycemia Symptom Recognition [ Time Frame: 4 weeks ]
    Participant's self-reported symptoms of hypoglycemia will be obtained during the initial hypoglycemic clamp study (Day 0) and during the second hypoglycemic clamp study (Day 28) following the 4-week intervention period.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
Ratio of Self-Reported Hypoglycemic Episodes to Total Hypoglycemic Episodes [ Time Frame: 6 weeks ]
Participants will complete a report of all hypoglycemic events during the study surveillance periods. The average ratio of self-reported hypoglycemic episodes to total hypoglycemic episodes recorded by Continuous Glucose Monitoring (CGM) during these periods will be compared between the study arms.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Restoration of Hypoglycemia Awareness With Metoclopramide
Official Title  ICMJE Restoration of Hypoglycemia Awareness With Metoclopramide
Brief Summary Metoclopramide is a drug approved by the FDA for gastroesophageal reflux and to relieve symptoms in adults with acute and recurrent diabetic gastroparesis. The objective of this study is to determine whether metoclopramide can improve hypoglycemia awareness and decrease the incidence of hypoglycemia in type 1 diabetes patients with hypoglycemia unawareness.
Detailed Description

Hypoglycemia is the most prevalent clinical complication in the daily management of diabetes and is the major obstacle to normalizing blood sugar. For people with Type 1 diabetes mellitus (T1DM), hypoglycemia associated autonomic failure (HAAF) increases the risk for severe hypoglycemia by a factor of 25 or more. A major component of HAAF is hypoglycemia unawareness (perhaps more accurately defined as impaired awareness of hypoglycemia), which involves in the loss/diminution of warning symptoms to hypoglycemia that would normally prompt a corrective behavioral response (e.g., eating food). Approximately 25-40% of people with T1DM report hypoglycemia unawareness. This value is most certainly an underestimation, as even people with diabetes who report having intact hypoglycemia, demonstrate impaired awareness of biochemically confirmed hypoglycemia. Although a major clinical problem for people with T1DM, it remains largely unknown what therapeutic agents could possibly be used to treat hypoglycemia unawareness.

With a goal of identifying existing biological compounds that could restore hypoglycemia awareness, laboratory drug screens were conducted using animal models. It was postulated that an ideal drug would markedly enhance the ability to sense hypoglycemia and trigger a potentially life-saving behavioral response (ie, alert the subject to increase food consumption). The vast majority of tested drugs did not restore hypoglycemia awareness (ie, did not restore blunted food intake response to hypoglycemia). Interestingly, of all the drugs tested, the dopamine antagonist metoclopramide consistently restored hypoglycemia awareness in several preclinical experiments. Additionally, metoclopramide also restored the impaired counterregulatory response to hypoglycemia in the animal model of HAAF.

This pilot phase II clinical trial (with placebo control) will be conducted to determine if FDA approved doses of Metaclopramdide can restore both, 1) hypoglycemia awareness, and 2) the sympathoadrenal response to hypoglycemia in patients with T1DM and hypoglycemia unawareness.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Hypoglycemia Unawareness
Intervention  ICMJE
  • Drug: Metoclopramide
    10 mg metoclopramide four times a day
  • Drug: Placebo
    10 mg matching placebo capsules four times a day
Study Arms  ICMJE
  • Experimental: T1DM - Unaware: Metoclopramide
    T1DM participants with hypoglycemia unawareness determined by a hypoglycemic clamp study will receive 10 mg metoclopramide four times a day during the four-week intervention period.
    Intervention: Drug: Metoclopramide
  • Placebo Comparator: T1DM - Unaware: Placebo
    T1DM participants with hypoglycemia unawareness determined by a hypoglycemic clamp study will receive 10 mg matching placebo capsules four times a day during the four-week intervention period.
    Intervention: Drug: Placebo
  • Placebo Comparator: T1DM - Aware: Placebo
    T1DM participants with hypoglycemia awareness determined by a hypoglycemic clamp study will receive 10 mg matching placebo capsules four times a day during the four-week intervention period.
    Intervention: Drug: Placebo
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2019)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with Type 1 Diabetes Mellitus
  • Diabetes duration > 5 years
  • Hemoglobin A1c ≤ 9%
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria:

  • History of myocardial infarction, cardiac arrhythmia, congestive heart failure and coronary artery insufficiency
  • History of stroke or brain disease
  • History of genitourinary obstruction or urinary retention
  • Advanced liver disease
  • Active anemia with hemoglobin less than 11 g/dL
  • Female in pregnancy or breastfeeding, or not able to practice effective contraception during the study period
  • Uncontrolled mania or active major depressive disorder
  • Previous allergic reaction or side effect to heparin use
  • Contraindications to metoclopramide or conditions raising the risk for complication development to metoclopramide, such as hypersensitivity to metoclopramide, ongoing mechanical gastrointestinal obstruction, uncontrolled hypertension, pheochromocytoma, seizure disorders, Parkinson's disease, use of neuroleptics or antipsychotics within 6 months, use of benzodiazepines within the last month, active or recent (last 14 days) use of monoamine oxidase inhibitors or opioids, active alcohol or drug abuse, or other sedatives
  • Participation in another study evaluating treatment for impaired awareness of hypoglycemia or hypoglycemia-associated autonomic failure in the last 30 days
  • Current use of unblinded real-time Continuous Glucose Monitoring System
  • Frequent need of acetaminophen administration
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sally Bradstreet 801-581-4684 sally.bradstreet@hsc.utah.edu
Contact: Simon Fisher, MD 801-581-7755 sfisher@u2m2.utah.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03970720
Other Study ID Numbers  ICMJE IRB_00118549
1R01DK118082-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Simon Fisher, University of Utah
Study Sponsor  ICMJE Simon Fisher
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Simon Fisher, MD University of Utah
PRS Account University of Utah
Verification Date May 2019

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