Restoration of Hypoglycemia Awareness With Metoclopramide

Last updated: May 8, 2025
Sponsor: Simon Fisher
Overall Status: Active - Recruiting

Phase

2

Condition

Hormone Deficiencies

Diabetes (Pediatric)

Treatment

Metoclopramide

Placebo

Clinical Study ID

NCT03970720
IRB_00118549
1R01DK118082-01A1
  • Ages 20-60
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 thatconforms to federal and institutional guidelines

Exclusion

Exclusion Criteria:

  • History of myocardial infarction, cardiac arrhythmia, congestive heart failure andcoronary 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 effectivecontraception 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 complicationdevelopment to metoclopramide, such as hypersensitivity to metoclopramide, ongoingmechanical gastrointestinal obstruction, uncontrolled hypertension,pheochromocytoma, seizure disorders, Parkinson's disease, use of neuroleptics orantipsychotics within 6 months, use of benzodiazepines within the last month, activeor recent (last 14 days) use of monoamine oxidase inhibitors or opioids, activealcohol or drug abuse, or other sedatives

  • Participation in another study evaluating treatment for impaired awareness ofhypoglycemia 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

Study Design

Total Participants: 36
Treatment Group(s): 2
Primary Treatment: Metoclopramide
Phase: 2
Study Start date:
May 28, 2019
Estimated Completion Date:
March 31, 2026

Study 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.

Connect with a study center

  • University of Kentucky

    Lexington, Kentucky 40516
    United States

    Active - Recruiting

  • University of Utah

    Salt Lake City, Utah 84132
    United States

    Completed

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.