Metoclopramide for Hypoglycemia Unawareness

Overseen By Karen M Shearer

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Simon Fisher

Must not be taking: Neuroleptics, Antipsychotics, Benzodiazepines, others

Disqualifiers: Cardiac disease, Stroke, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot participate if you have used neuroleptics or antipsychotics in the last 6 months, benzodiazepines in the last month, or monoamine oxidase inhibitors or opioids in the last 14 days.

How does the drug metoclopramide differ from other treatments for hypoglycemia unawareness?

Metoclopramide is unique because it is primarily known for its ability to enhance gastric emptying and increase gastrointestinal motility, which is different from typical treatments for hypoglycemia unawareness. While it is not a standard treatment for this condition, its use in this context may be novel due to its effects on the digestive system, potentially influencing blood sugar levels. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Metoclopramide for hypoglycemia unawareness?

The research does not provide direct evidence supporting the effectiveness of Metoclopramide for hypoglycemia unawareness. However, Metoclopramide is known to stimulate prolactin release, which may have indirect effects on hormone regulation. ^{6 7 8 9 10}

Who Is on the Research Team?

Simon Fisher, MD, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for adults with Type 1 Diabetes Mellitus, who have had diabetes for over 5 years and are experiencing low blood sugar without the usual warning signs. Participants must not be pregnant or breastfeeding, should not have severe heart, liver, or brain conditions, and cannot be on certain medications like antipsychotics or opioids.

Inclusion Criteria

I have Type 1 Diabetes Mellitus.

Your hemoglobin A1c level is less than or equal to 9%.

Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria

My liver disease is in an advanced stage.

My hemoglobin level is below 11 g/dL.

I cannot take metoclopramide due to allergies, certain health conditions, or recent use of specific medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either metoclopramide or placebo for 4 weeks to assess restoration of hypoglycemia awareness

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including self-reported hypoglycemic episodes

2 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Metoclopramide
• Placebo

Trial Overview The study is testing whether Metoclopramide can help people with type 1 diabetes become more aware of when their blood sugar gets too low. It involves comparing Metoclopramide to a placebo (a substance with no active drug) to see if it reduces episodes of low blood sugar.

How Is the Trial Designed?

Group I: T1DM - Unaware: Metoclopramide Experimental Treatment 1 Intervention

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.

Group II: T1DM - Aware: Placebo Placebo Group 1 Intervention

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.

Group III: T1DM - Unaware: Placebo Placebo Group 1 Intervention

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.

Metoclopramide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Metoclopramide for:

• Gastroesophageal reflux disease (GERD)
• Diabetic gastroparesis
• Prevention of chemotherapy-induced nausea and vomiting

Approved in European Union as Metoclopramide for:

• Symptomatic treatment of nausea and vomiting
• Prevention of delayed chemotherapy-induced nausea and vomiting
• Treatment of gastroparesis

Approved in Canada as Metoclopramide for:

• Symptomatic treatment of nausea and vomiting
• Prevention of chemotherapy-induced nausea and vomiting
• Treatment of gastroparesis

Who Is Running the Clinical Trial?

Simon Fisher

Lead Sponsor

Trials

1

Recruited

40+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 90 type 1 diabetic patients, those with hypoglycemia unawareness showed significantly lower adherence to insulin regimen changes (53.8%) compared to those with awareness (87.0%), indicating a challenge in managing their condition effectively.

Patients with hypoglycemia unawareness were older, had longer diabetes duration, and reported more severe hypoglycemic episodes, suggesting that targeted therapies to improve adherence and restore awareness could help reduce the risk of severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoglycemia unawareness is associated with reduced adherence to therapeutic decisions in patients with type 1 diabetes: evidence from a clinical audit. Smith, CB., Choudhary, P., Pernet, A., et al.[2022]

In a study of eight children, metoclopramide (MCP) did not significantly increase growth hormone (GH) levels, indicating it is not an effective test for diagnosing growth hormone deficiency.

MCP did stimulate prolactin (PRL) release in all subjects and caused a significant increase in cortisol levels after 5 hours, although cortisol levels remained within the normal range.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of arginine, insulin and metoclopramide on growth hormone, prolactin and cortisol release in children. Ijaiya, K., Roth, B., Schwenk, A.[2019]

New glucagon formulations, such as nasal powder and liquid-stable glucagon, have improved ease of use and are designed to be more effective in emergency situations for treating severe hypoglycemia in diabetic patients.

These newer formulations address the historical challenges of glucagon administration, which was often underutilized due to the complexity of reconstitution and concerns about safety, thereby enhancing patient confidence in emergency care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon: Its evolving role in the management of hypoglycemia. Isaacs, D., Clements, J., Turco, N., et al.[2022]

In a simulated user experience study with 39 participants, nasal glucagon (NG) administration was significantly more successful (89.5% vs 26.3%) and quicker (mean time of 23.9 seconds vs 207.3 seconds) compared to intramuscular glucagon (IMG) among caregivers.

Nasal glucagon was also found to be easy to use, with 80% of third parties and all caregivers expressing confidence in using it during real emergencies, indicating its potential as a preferred option for treating severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usability of Nasal Glucagon Device: Partially Randomized Caregiver and Third-Party User Experience Trial with Simulated Administration at a Japanese Site. Aranishi, T., Nagai, Y., Takita, Y., et al.[2020]

Intranasal (IN) glucagon has been successfully used in a prehospital setting to treat insulin-induced hypoglycemia, demonstrating its effectiveness in quickly reversing low blood sugar episodes.

This method of administration is particularly beneficial when intravenous (IV) access is difficult, as IN glucagon is as effective as IV glucagon and offers a rapid solution for hypoglycemic emergencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful administration of intranasal glucagon in the out-of-hospital environment. Sibley, T., Jacobsen, R., Salomone, J.[2013]

Administering maltose-sweetened drinks 2 hours before surgery effectively prevents hypoglycemia in young children undergoing general anesthesia, as shown in a study of 28 patients.

The maltose-treated group had significantly higher postoperative blood sugar levels (100±22 mg/ml) compared to a starved control group (22 patients), indicating the efficacy of this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypglycaemia in paediatric anaesthesia: The influence of metoclopramide and oral maltose in paediatric surgical patients. Fry, EN., Ibrahim, AA.[2019]

Metoclopramide is effective in treating conditions like diabetic gastroparesis and severe gastroesophageal reflux by increasing lower esophageal sphincter pressure and speeding up gastric emptying, making it a valuable option in postoperative care as well.

While metoclopramide is a powerful antiemetic used in cancer chemotherapy, it is not intended for long-term use, with oral therapy recommended for only 4 to 12 weeks and parenteral use limited to 1-2 days due to potential side effects like restlessness and drowsiness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metoclopramide: a dopamine receptor antagonist. DiPalma, JR.[2013]

Metoclopramide effectively enhances gastric emptying and gastrointestinal mobility by increasing contractions in the esophagus and stomach, making it useful for facilitating procedures like intubation and treating diabetic gastroparesis.

The drug is generally safe with mild and reversible side effects, but it should not be used with certain medications or in patients with specific medical conditions, highlighting the importance of careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of a new gastrointestinal drug--metoclopramide. Ponte, CD., Nappi, JM.[2013]

In a study involving 16 lung cancer patients undergoing cisplatin chemotherapy, a combination of metoclopramide and methylprednisolone effectively prevented vomiting in 70% of chemotherapy courses, demonstrating high efficacy as an antiemetic.

The treatment was well-tolerated with minimal side effects, including mild sleepiness in nine patients, diarrhea in three, and hiccups in three, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antiemetic combination of metoclopramide and methylprednisolone for cisplatin-induced vomiting]. Saito, H., Amano, H., Yasuda, Y., et al.[2013]

In a study evaluating the effects of metoclopramide on motion sickness, doses of 10 or 20 mg administered 75 minutes before exposure to stressors like parabolic flight or rotational chair stimulation did not significantly prevent nausea or vomiting.

Despite metoclopramide's known effectiveness as an antiemetic for other conditions, such as chemotherapy-induced nausea, it was ineffective in this context of motion sickness, indicating that its mechanism may not apply to all types of nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Failure of metoclopramide to control emesis or nausea due to stressful angular or linear acceleration. Kohl, RL.[2013]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Hypoglycemia unawareness is associated with reduced adherence to therapeutic decisions in patients with type 1 diabetes: evidence from a clinical audit. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The effects of arginine, insulin and metoclopramide on growth hormone, prolactin and cortisol release in children. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Glucagon: Its evolving role in the management of hypoglycemia. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Usability of Nasal Glucagon Device: Partially Randomized Caregiver and Third-Party User Experience Trial with Simulated Administration at a Japanese Site. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Successful administration of intranasal glucagon in the out-of-hospital environment. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Hypglycaemia in paediatric anaesthesia: The influence of metoclopramide and oral maltose in paediatric surgical patients. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Metoclopramide: a dopamine receptor antagonist. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Review of a new gastrointestinal drug--metoclopramide. [2013]

9. Japan pubmed.ncbi.nlm.nih.gov

[Antiemetic combination of metoclopramide and methylprednisolone for cisplatin-induced vomiting]. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Failure of metoclopramide to control emesis or nausea due to stressful angular or linear acceleration. [2013]