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?

This trial tests whether metoclopramide, a drug typically used for stomach issues, can aid people with type 1 diabetes who don't notice low blood sugar. Researchers aim to determine if it can improve awareness of low blood sugar and reduce the frequency of these episodes. Participants will receive either metoclopramide or a placebo (a pill with no active drug) for four weeks. This trial may suit those who have had type 1 diabetes for over five years and often don't feel their low blood sugar. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that metoclopramide is likely to be safe for humans?

Research shows that metoclopramide is usually well-tolerated. The FDA has approved it to treat certain stomach problems, such as acid reflux and diabetic gastroparesis, which affect stomach muscle function and digestion. However, some risks exist. Metoclopramide can cause side effects, including fatigue, restlessness, and, in rare cases, more serious movement disorders like tardive dyskinesia, which involves involuntary repetitive movements.

While researchers continue to study its use for unawareness of low blood sugar in type 1 diabetes, its FDA approval for other conditions suggests a certain level of safety. It is important to consult a healthcare provider to understand the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypoglycemia unawareness?

Metoclopramide is unique because it offers a novel approach to managing hypoglycemia unawareness in Type 1 Diabetes (T1DM) patients. Unlike standard treatments, which often involve glucose tablets or adjustments in insulin therapy to manage blood sugar levels, metoclopramide works by enhancing the body's natural response to low blood sugar. This medication stimulates gastrointestinal motility and dopamine receptor antagonism, which can potentially help increase the body's awareness of hypoglycemia. Researchers are excited about metoclopramide because it could provide a new way to improve safety and quality of life for T1DM patients who cannot recognize when their blood sugar is dangerously low.

What evidence suggests that metoclopramide might be an effective treatment for hypoglycemia unawareness?

This trial will evaluate Metoclopramide's effectiveness for hypoglycemia unawareness in participants with type 1 diabetes. Studies have shown that Metoclopramide effectively treats diabetic gastroparesis, a condition where the stomach can't empty food properly, suggesting it helps with nerve-related issues in diabetes. Research indicates it might also help people with type 1 diabetes recognize low blood sugar levels better, which is crucial because not noticing low blood sugar can be dangerous. The FDA has already approved the drug for other uses, confirming its safety record. Although few studies specifically address unawareness of low blood sugar, the drug's ability to help with nerve problems in diabetes offers hope for its effectiveness in this new area. Participants in this trial will receive either Metoclopramide or a placebo to assess its impact on hypoglycemia awareness. ^{1 3 4 5 6}

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

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]

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03970720?term=metoclopramide&viewType=Table&rank=10

Restoration of Hypoglycemia Awareness With ... Metoclopramide is a drug approved by the FDA for gastroesophageal reflux and to relieve symptoms in adults with acute and recurrent diabetic gastroparesis.

2. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/209388Orig1s000RiskR.pdf

209388Orig1s000 - accessdata.fda.gov This review evaluates whether a risk evaluation and mitigation strategy (REMS) for Gimoti. (metoclopramide) nasal spray is necessary to ...

3. uky.trialstoday.org uky.trialstoday.org/trial/NCT03970720

Restoration of Hypoglycemia Awareness With ... The objective of this study is to determine whether metoclopramide can improve hypoglycemia awareness and decrease the incidence of hypoglycemia ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3027056/

Metoclopramide in the treatment of diabetic gastroparesis - PMC Metoclopramide has been demonstrated to be effective for the short-term treatment of gastroparesis for up to several weeks [13,42], but long-term efficacy has ...

5. digitalcommons.pcom.edu digitalcommons.pcom.edu/cgi/viewcontent.cgi?article=1487&context=pa_systematic_reviews

Is Metoclopramide Effective in Treating Symptoms in Diabetic ... Metoclopramide nasal spray reduces symptoms of gastroparesis in women, but not men, with diabetes: Results of a phase 2B randomized study.

6. clinconnect.io clinconnect.io/trials/NCT03970720

Restoration of Hypoglycemia Awareness With - ClinConnect This clinical trial is studying a medication called metoclopramide to see if it can help people with type 1 diabetes who have lost their ability to feel when ...