A Phase 2 interventional study of Metoclopramide and Placebo in Hypoglycemia Unawareness, sponsored by Simon Fisher. Recruiting at 2 sites in United States. Open to participants aged 20 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-03-20.
Sponsored by Simon Fisher · Phase 2, Interventional, and Treatment
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.
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.
3,522 studies on the registry are indexed under Diabetes Mellitus, Type 1; 577 are open to participants now.
This study's planned enrollment of 36 is close to the median of 40 across 2,649 interventional studies indexed under Diabetes Mellitus, Type 1.
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Exclusion Criteria:
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.
Drug: Metoclopramide
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.
Drug: 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.
Drug: Placebo
10 mg metoclopramide four times a day
10 mg matching placebo capsules four times a day
Change in Blood Glucagon
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.
Time frame: 4 weeks
Change in Blood Epinephrine
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.
Time frame: 4 weeks
Change in Blood Norepinephrine
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.
Time frame: 4 weeks
Change in Blood Cortisol
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.
Time frame: 4 weeks
Change in Blood Pancreatic Polypeptide
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.
Time frame: 4 weeks
Change in Hypoglycemia Symptom Recognition
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.
Time frame: 4 weeks
Ratio of Self-Reported Hypoglycemic Episodes to Total Hypoglycemic Episodes
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.
Time frame: 6 weeks
Plan to share: No
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