Restoration of Hypoglycemia Awareness With Metoclopramide

NCT03970720 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: IRB_001185491R01DK118082-01A1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

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.

Conditions

Hypoglycemia Unawareness

Keywords

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  4 weeks

Secondary Outcomes (1)

• Ratio of Self-Reported Hypoglycemic Episodes to Total Hypoglycemic Episodes

  6 weeks

Study Arms (3)

T1DM - Unaware: Metoclopramide

EXPERIMENTAL

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 - Unaware: Placebo

PLACEBO COMPARATOR

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 - Aware: Placebo

PLACEBO COMPARATOR

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

Interventions

Metoclopramide DRUG

10 mg metoclopramide four times a day

T1DM - Unaware: Metoclopramide

Placebo DRUG

10 mg matching placebo capsules four times a day

T1DM - Aware: Placebo; T1DM - Unaware: Placebo

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Simon Fisher: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

University of Kentucky

Lexington, Kentucky, 40516, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84132, United States

COMPLETED

Related Publications (9)

• Cryer PE. Hypoglycemia-associated autonomic failure in diabetes. Handb Clin Neurol. 2013;117:295-307. doi: 10.1016/B978-0-444-53491-0.00023-7.

  PMID: 24095133 BACKGROUND

• Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2013 Jul 25;369(4):362-72. doi: 10.1056/NEJMra1215228. No abstract available.

  PMID: 23883381 BACKGROUND

• Heller SR, Cryer PE. Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans. Diabetes. 1991 Feb;40(2):223-6. doi: 10.2337/diab.40.2.223.

  PMID: 1991573 BACKGROUND

• Schultes B, Schmid SM, Wilms B, Jauch-Chara K, Oltmanns KM, Hallschmid M. Lactate infusion during euglycemia but not hypoglycemia reduces subsequent food intake in healthy men. Appetite. 2012 Jun;58(3):818-21. doi: 10.1016/j.appet.2012.01.022. Epub 2012 Jan 28.

  PMID: 22314041 BACKGROUND

• Schmid SM, Jauch-Chara K, Hallschmid M, Oltmanns KM, Born J, Schultes B. Short-term nocturnal hypoglycaemia increases morning food intake in healthy humans. Diabet Med. 2008 Feb;25(2):232-5. doi: 10.1111/j.1464-5491.2007.02347.x.

  PMID: 18290864 BACKGROUND

• Dewan S, Gillett A, Mugarza JA, Dovey TM, Halford JC, Wilding JP. Effects of insulin-induced hypoglycaemia on energy intake and food choice at a subsequent test meal. Diabetes Metab Res Rev. 2004 Sep-Oct;20(5):405-10. doi: 10.1002/dmrr.471.

  PMID: 15343587 BACKGROUND

• Towler DA, Havlin CE, Craft S, Cryer P. Mechanism of awareness of hypoglycemia. Perception of neurogenic (predominantly cholinergic) rather than neuroglycopenic symptoms. Diabetes. 1993 Dec;42(12):1791-8. doi: 10.2337/diab.42.12.1791.

  PMID: 8243825 BACKGROUND

• Geddes J, Schopman JE, Zammitt NN, Frier BM. Prevalence of impaired awareness of hypoglycaemia in adults with Type 1 diabetes. Diabet Med. 2008 Apr;25(4):501-4. doi: 10.1111/j.1464-5491.2008.02413.x.

  PMID: 18387080 BACKGROUND

• Kubiak T, Hermanns N, Schreckling HJ, Kulzer B, Haak T. Assessment of hypoglycaemia awareness using continuous glucose monitoring. Diabet Med. 2004 May;21(5):487-90. doi: 10.1111/j.1464-5491.2004.1136.x.

  PMID: 15089796 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Metoclopramide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Study Officials

• Simon Fisher, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simon Fisher, MD, PhD

CONTACT

859-562-0473; sjfi230@uky.edu

Karen M Shearer

CONTACT

859-323-7778; Karen.Shearer@uky.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: May 31, 2019
• Study Start: May 28, 2019
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)