Oral Carbohydrates for Hypoglycemia in Type 1 Diabetes

(REMODAL Trial)

Recruiting at 1 trial location

Overseen By Valérie Boudreau, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Institut de Recherches Cliniques de Montreal

Must be taking: Insulin

Disqualifiers: Gastroparesis, Cardiac abnormalities, Epilepsy, others

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods to treat mild low blood sugar (hypoglycemia) in individuals with Type 1 diabetes. Researchers aim to determine if administering small amounts of oral carbohydrates earlier, at a blood sugar level of 5.0 mmol/L, can more effectively prevent severe drops compared to waiting until it falls below 4.0 mmol/L. The study seeks to reduce the frequency of low blood sugar episodes and enhance overall well-being without significantly increasing calorie intake. Individuals who have had Type 1 diabetes for at least a year and are using insulin therapy may be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to innovative diabetes management strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants should not have anticipated treatment changes during the trial period. This might mean you should continue your current treatment without changes.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that oral carbohydrates are generally safe for people with Type 1 diabetes. Some studies found that consuming carbohydrates before surgery is safe and beneficial for those with diabetes, enhancing bodily function.

This trial tests different carbohydrate amounts, commonly used in diabetes care to control blood sugar levels. They are usually well-tolerated, with no major reports of serious side effects from this use.

The trial uses doses of 8 grams and 16 grams, typical for managing low blood sugar. Overall, evidence suggests that oral carbohydrates are safe and effective for preventing low blood sugar in people with Type 1 diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these approaches to treat hypoglycemia in Type 1 diabetes because they explore proactive carbohydrate administration, which is different from the traditional reactive methods. The standard practice typically involves giving carbohydrates only when blood sugar levels drop below 4.0 mmol/L. However, this trial is testing giving 8 or 16 grams of carbohydrates earlier, at 5.0 mmol/L, to prevent hypoglycemia before it occurs. This proactive strategy could potentially reduce the frequency and severity of hypoglycemic events while also minimizing unnecessary calorie intake. By shifting to a more anticipatory approach, these methods aim to enhance overall blood sugar management and improve daily life for people with Type 1 diabetes.

What evidence suggests that this trial's treatments could be effective for hypoglycemia in Type 1 diabetes?

This trial will compare different approaches to using oral carbohydrates for managing hypoglycemia in individuals with Type 1 Diabetes. Studies have shown that mild hypoglycemia, or low blood sugar, can be effectively treated by eating glucose tablets, which quickly raise blood sugar levels and manage symptoms rapidly. Research indicates that continuous glucose monitoring (CGM) can better manage blood sugar by reducing episodes of low blood sugar. In this trial, one arm will follow a reactive approach, administering 16 grams of carbohydrates when CGM readings fall below 4.0 mmol/L. Another arm will test a proactive approach, providing 8 grams of carbohydrates at a higher glucose level of 5.0 mmol/L, while a third arm will administer 16 grams at the same proactive threshold. The American Diabetes Association supports using glucose tablets because they effectively increase blood sugar levels quickly. This method may help stabilize blood sugar and reduce the frequency of low blood sugar episodes. ^{6 7 8 9 10}

Who Is on the Research Team?

Remi Rabasa-Lhoret

Principal Investigator

IRCM

Are You a Good Fit for This Trial?

This trial is for individuals with Type 1 Diabetes who regularly monitor their blood sugar using CGM. It's designed to find better ways to prevent and treat low blood sugar episodes. Participants should be willing to try different carbohydrate amounts when their sugar levels drop.

Inclusion Criteria

HbA1c level below 9.0%

I am currently managing my diabetes with insulin injections or an insulin pump.

I am either male or female and use an insulin pump or injections for diabetes management.

Exclusion Criteria

I have serious heart rhythm problems.

I have gastroparesis.

I haven't had major blood vessel problems or low potassium levels in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive different carbohydrate interventions to manage hypoglycemia using CGM technology

6 weeks

Multiple visits for each intervention

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oral Carbohydrate

Trial Overview The REMODAL trial is testing if taking a smaller amount of carbohydrates at an earlier sign of dropping blood sugar (5.0 mmol/L) can help avoid hypoglycemia more effectively than the usual method of waiting until it falls below 4.0 mmol/L.

How Is the Trial Designed?

Group I: 8g CHO at 5.0 mmol/L (Proactive Approach) Experimental Treatment 1 Intervention

Participants receive 8 grams of carbohydrate when their CGM reading reaches a proactive threshold of 5.0 mmol/L. This arm tests whether a lower amount of CHO, administered at a higher glucose level, can effectively prevent hypoglycemia with minimal caloric intake.

Group II: 16g CHO at 5.0 mmol/L (Proactive Approach) Experimental Treatment 1 Intervention

Participants receive 16 grams of carbohydrate at the proactive threshold of 5.0 mmol/L. This arm examines if a slightly higher dose of CHO at the same proactive threshold provides additional preventive benefits compared to 8 grams, while still aiming to avoid hypoglycemia and limit subsequent glucose fluctuations.

Group III: 16g CHO at < 4.0 mmol/L (Reactive Approach) Placebo Group 1 Intervention

Participants receive 16 grams of carbohydrate only when their CGM reading falls below 4.0 mmol/L, in line with the traditional "reactive" approach. This arm serves as a control, reflecting current hypoglycemia treatment guidelines, allowing comparison to proactive interventions.

Who Is Running the Clinical Trial?

Institut de Recherches Cliniques de Montreal

Lead Sponsor

Trials

72

Recruited

10,300+

Published Research Related to This Trial

Dasiglucagon demonstrated a significantly faster recovery from severe hypoglycemia in adults with type 1 diabetes, with a median recovery time of just 10 minutes compared to 40 minutes for placebo, and similar to 12 minutes for reconstituted glucagon.

The safety profile of dasiglucagon was comparable to that of reconstituted glucagon, with nausea and vomiting being the most common side effects, indicating it is a reliable and effective treatment option for severe hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasiglucagon-A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical Trial. Pieber, TR., Aronson, R., Hövelmann, U., et al.[2022]

Intranasal glucagon is effective in treating severe hypoglycemia in patients with diabetes, showing a rapid increase in blood glucose levels within 15-30 minutes, similar to injectable glucagon, based on a systematic review of 10 studies.

Most caregivers preferred intranasal glucagon due to its ease of use, with administration times significantly faster than injectable forms, highlighting its potential for improving emergency treatment in disoriented or unconscious patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Usability of Intranasal Glucagon for the Management of Hypoglycemia in Patients With Diabetes: A Systematic Review. Singh-Franco, D., Moreau, C., Levin, AD., et al.[2021]

For treating nonsevere hypoglycemia in adults with insulin-treated diabetes, a dose of 15 to 20 grams of oral glucose is generally effective, but this may need to be adjusted based on individual factors like body weight and insulin delivery methods.

Current guidelines for hypoglycemia treatment may need to be updated to reflect the advancements in insulin therapies and continuous glucose monitoring, as the standard recommendation has not changed despite these developments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal Carbohydrate Dose for Treatment of Nonsevere Hypoglycemia in Insulin-Treated Patients With Diabetes: A Narrative Review. Urbanová, J., Frier, BM., Taniwall, A., et al.[2022]

In both rat experiments and a clinical study with 23 type 1 diabetic patients, the combination of oral glucose and glycerol was more effective in promoting glucose recovery during hypoglycemia than glucose alone.

This study suggests that adding glycerol to glucose could enhance treatment options for managing hypoglycemia in diabetic patients, based on a systematic comparison over a 4-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycerol Potentiates the Effects of Glucose in Promoting Glucose Recovery During Hypoglycemia: From Basic to Clinical Investigations and Their Therapeutic Application. Eik Filho, W., Wanczinski Ferrari, BJ., Masetto Antunes, M., et al.[2021]

In a study involving patients with Type 1 Diabetes (T1D) using insulin pumps with predictive suspension technology, administering 10 grams of sucrose for hypoglycemia was less effective than the standard 15 grams, as evidenced by lower blood glucose levels after treatment.

The results indicated that 21% of patients in the 10-gram group needed to repeat treatment after 15 minutes, while none in the 15-gram group did, suggesting that the standard dose of sucrose remains necessary for effective hypoglycemia management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lower versus standard sucrose dose for treating hypoglycemia in patients with type 1 diabetes mellitus in therapy with predictive low glucose suspend (PLGS) augmented insulin pumps: A randomized crossover trial in Santiago, Chile. Grassi, B., Onetto, MT., Zapata, Y., et al.[2021]

In a study involving 10 adults with type 1 diabetes, the use of a predictive low-glucose suspend (PLGS) system resulted in fewer carbohydrate (CHO) treatments for hypoglycemia, with a median of only 9g CHO needed during hypoglycemic events.

The findings suggest that current guidelines recommending 15-20g of CHO for treating mild to moderate hypoglycemia may need to be updated, as lower amounts may be sufficient during insulin suspensions to prevent rebound hyperglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive Low-Glucose Suspend Necessitates Less Carbohydrate Supplementation to Rescue Hypoglycemia: Need to Revisit Current Hypoglycemia Treatment Guidelines. Pinsker, JE., Bartee, A., Katz, M., et al.[2022]

Participants with type 1 diabetes following a low carbohydrate diet (75 g per day) showed significant improvements in glycaemic control, with HbA1c levels decreasing from 63 to 55 mmol/mol (8.9% to 8.2%) and daily insulin use dropping from 64.4 to 44.2 units/day over 12 weeks.

The study suggests that a low carbohydrate diet can be a practical approach for managing type 1 diabetes, potentially reducing insulin requirements and aiding in weight loss, without negatively impacting other health markers like blood pressure or lipid profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised trial of the feasibility of a low carbohydrate diet vs standard carbohydrate counting in adults with type 1 diabetes taking body weight into account. Krebs, JD., Parry Strong, A., Cresswell, P., et al.[2022]

In a study analyzing 40 nonsevere hypoglycemia episodes in type 1 diabetes patients using automated insulin delivery (AID) systems, the standard recommendation of 15 g of carbohydrates every 15 minutes was found to be neither excessive nor optimal for treatment.

After consuming carbohydrates, plasma glucose levels increased by an average of 0.9 mmol/L after 15 minutes, with 45% of episodes recovering to a safe level, indicating that while the guidelines are effective, there may be room for optimization based on the type of AID system used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes Using Oral Carbohydrates During Automated Insulin Delivery With and Without Glucagon. Taleb, N., Cheng, R., Wu, Z., et al.[2023]

In a study involving 3 children with type 1 diabetes, small doses of subcutaneous glucagon effectively prevented severe hypoglycemia when the children refused to eat, with blood glucose levels rising significantly after administration.

The glucagon was well tolerated, with only mild nausea reported, and none of the children required hospitalization for hypoglycemia, indicating that this approach is both safe and effective for managing hypoglycemic episodes in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mini-doses of glucagon to prevent hypoglycemia in children with type 1 diabetes refusing food: a case series. Tinti, D., Rabbone, I.[2020]

In a study involving 33 children with type 1 diabetes, both glucose and sucrose (from Skittles) were found to be equally effective in treating hypoglycemia, while fructose was significantly less effective.

Post-study, a majority of children preferred glucose or sucrose as their treatment options, indicating that effective and more affordable treatments like Skittles could be beneficial for managing hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes. Husband, AC., Crawford, S., McCoy, LA., et al.[2013]

Lispro, a newly FDA-approved insulin analog, leads to lower post-meal blood sugar levels compared to regular human insulin, but it also has a higher risk of causing hypoglycemia, especially when carbohydrate intake is low.

In a study involving 12 individuals with insulin-dependent diabetes mellitus (IDDM), those using lispro experienced more frequent and rapid hypoglycemia, indicating that patients switching to lispro should closely monitor their blood sugar levels and possibly adjust their carbohydrate intake or insulin dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. Burge, MR., Castillo, KR., Schade, DS.[2019]

Intranasal (IN) glucagon is a newly approved, safe, and effective treatment for hypoglycemia in patients aged 4 years and older, showing over 98% success in treating hypoglycemic events, comparable to intramuscular (IM) glucagon.

IN glucagon can be administered quickly (in less than a minute) without the need for reconstitution, making it a convenient needle-free option for those uncomfortable with injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Glucagon: A New Way to Treat Hypoglycemic Emergencies. Lowe, RN., Trujillo, JM.[2020]

A systematic review of nine studies on low-carbohydrate diets for managing type 1 diabetes found that while some studies reported significant reductions in HbA1c, the overall effect was inconclusive due to significant variability among the studies.

The review highlights the need for more rigorous primary studies to better understand the impact of low-carbohydrate diets on diabetes management, as current evidence is limited and mixed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. Turton, JL., Raab, R., Rooney, KB.[2022]

In a study involving 39 children with type 1 diabetes, jellybeans were found to be the least effective treatment for hypoglycemia, requiring more repeat doses compared to glucose tablets, orange juice, and sugar mints.

Glucose tablets, Mentos dragees®, and orange juice showed similar efficacy in resolving hypoglycemia, with most children needing about 15 minutes for their blood glucose levels to normalize after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective treatment of hypoglycemia in children with type 1 diabetes: a randomized controlled clinical trial. McTavish, L., Wiltshire, E.[2013]

Citations

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Treatment of Mild Hypoglycemia - PMC Historically, it has been reported that mild hypoglycemia episodes can be effectively treated by ingestion of oral glucose or carbohydrate-containing foods such ...

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Managing Impending Nonsevere Hypoglycemia With Oral ... Overall, CGM technology improves glucose management, namely, hypoglycemia reduction (13). By gaining insights into glycemic fluctuations with ...

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Can glucose tablets help with managing hypoglycemia? The American Diabetes Association (ADA) notes that glucose tablets are an effective option for rapidly increasing blood sugar levels. However, ...

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Everything You Need to Know About Glucose Tablets These tablets are a convenient source of carbohydrates, offering a pre-measured dose to help quickly restore blood sugar to the target range.

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Not all sugars are the same: Using glucose to treat ... Most glucose tablets contain 4 grams of carbs each and it's typically recommended that you eat 4 tablets (16 carbs) while experiencing a low.

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Carbohydrate Restriction in Type 1 Diabetes: A Realistic ... Low carbohydrate diets (LCD; <130 g/day) may represent a means to improve glycaemic control and metabolic health in people with T1D.

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Novel oral glucose‐lowering drugs are associated with ... Novel oral GLD treatment was associated with lower risk of all‐cause mortality, CVD and severe hypoglycaemia compared with insulin treatment.

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Study Details | NCT01035801 | Safety, Tolerability, ... This study will also tell whether single tablet of IN-105 is safe for patients with Type 1 diabetes mellitus who are currently taking insulin injections.

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9. Pharmacologic Approaches to Glycemic Treatment Injectable and oral glucose-lowering medications have been studied for their efficacy as adjunct to insulin treatment of type 1 diabetes.

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Clinical effectiveness and safety of preoperative oral ... On the other hand, some studies have shown that preoperative oral carbohydrate intake is safe and feasible for people with diabetes and can improve ...