Oral Carbohydrates for Hypoglycemia in Type 1 Diabetes
(REMODAL Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byRemi Rabasa-Lhoret
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Institut de Recherches Cliniques de Montreal
Must be taking: Insulin
Disqualifiers: Gastroparesis, Cardiac abnormalities, Epilepsy, others
Trial Summary
What is the purpose of this trial?
The REMODAL trial is a randomized crossover study aiming to update treatment guidelines for mild hypoglycemia in people with Type 1 diabetes using continuous glucose monitoring (CGM) technology. The study will assess whether treating mild hypoglycemia proactively (at a glucose threshold of 5.0 mmol/L) with lower doses of carbohydrate (CHO) is more effective than the traditional reactive approach (treatment at \< 4.0 mmol/L). The goal is to reduce hypoglycemia frequency and improve quality of life, while minimizing caloric intake and rebound hyperglycemia.
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.
What data supports the effectiveness of the treatment Oral Carbohydrate for hypoglycemia in Type 1 Diabetes?
Research shows that oral carbohydrates like glucose, sucrose, and fructose are effective in treating hypoglycemia (low blood sugar) in children with type 1 diabetes. Additionally, current guidelines recommend using 15-20 grams of carbohydrates to manage mild to moderate hypoglycemia, although some studies suggest that less may be needed in certain situations.12345
Is oral carbohydrate safe for treating hypoglycemia in type 1 diabetes?
How does the oral carbohydrate treatment for hypoglycemia in type 1 diabetes differ from other treatments?
The oral carbohydrate treatment for hypoglycemia in type 1 diabetes is unique because it involves the use of simple carbohydrates, like glucose, which are rapidly absorbed to quickly raise blood sugar levels. This approach is different from other treatments like glucagon injections, which are used when oral carbohydrates cannot be administered, such as in cases of nausea or food refusal.611121314
Eligibility Criteria
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
I am 18 years old or older.
HbA1c level below 9.0%
I am currently managing my diabetes with insulin injections or an insulin pump.
See 2 more
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.
See 6 more
Trial Timeline
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
Treatment Details
Interventions
- Oral Carbohydrate (Other)
Trial OverviewThe 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.
Participant Groups
3Treatment groups
Experimental Treatment
Placebo Group
Group I: 8g CHO at 5.0 mmol/L (Proactive Approach)Experimental Treatment1 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 Treatment1 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 Group1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Institut de recherches cliniques de MontréalMontreal, Canada
Montreal Clinical Research InstituteMontreal, Canada
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Who Is Running the Clinical Trial?
Institut de Recherches Cliniques de MontrealLead Sponsor
References
Low-carbohydrate diets for type 1 diabetes mellitus: A systematic review. [2022]Type 1 diabetes is an autoimmune condition characterised by pancreatic beta cell destruction and absolute insulin deficiency. The strongest predictor of diabetes complications is glycaemic control and achieving HbA1c ≤ 7.0% is the primary management target. However, standard treatment appears to be lacking and adjunctive strategies require consideration. A systematic review was conducted to examine the effect of low-carbohydrate diets on type 1 diabetes management. Four databases were searched from inception until 28 March 2017: MEDLINE; CINAHL; Cochrane Library; and EMBASE. All primary studies containing a methods section (excluding cross-sectional) were included. Reports had to quantitatively measure the effect(s) of a dietary intervention or observed intake over at least two weeks where carbohydrate is below 45% total energy in adults and/or children with type 1 diabetes. The primary outcome was HbA1c and secondary outcomes were severe hypoglycaemia, total daily insulin, BMI, quality of life and mean daily glucose. Seventy-nine full-text articles were assessed for eligibility and nine were included (two randomised controlled trials, four pre-post interventions, two case-series, one case-report). Eight studies reported a mean change in HbA1c with a low-carbohydrate diet. Of these, four reported a non-significant change (P ≥ 0.05) and three reported statistically significant reductions (P
Predictive Low-Glucose Suspend Necessitates Less Carbohydrate Supplementation to Rescue Hypoglycemia: Need to Revisit Current Hypoglycemia Treatment Guidelines. [2022]Current guidelines recommend 15-20 g of carbohydrate (CHO) for treatment of mild to moderate hypoglycemia. However, these guidelines do not account for reduced insulin during suspensions with predictive low-glucose suspend (PLGS). We assessed insulin suspensions, hypoglycemic events, and CHO treatment during a 20-h inpatient evaluation of an investigational system with a PLGS feature, including an overnight basal up-titration period to activate the PLGS. Among 10 adults with type 1 diabetes, there were 59 suspensions; 7 suspensions were associated with rescue CHO and 5 with hypoglycemia. Rescue treatment consisted of median 9 g CHO (range: 5-16 g), with no events requiring repeat CHO. No rescue CHO were given during or after insulin suspension for the overnight basal up-titration. To minimize rebound hyperglycemia and needless calorie intake from hypoglycemia overtreatment, updated guidance for PLGS systems should reflect possible need to reduce CHO amounts for hypoglycemia rescue associated with an insulin suspension. The clinical trial was registered with ClinicalTrials.gov (NCT03890003).
Effective treatment of hypoglycemia in children with type 1 diabetes: a randomized controlled clinical trial. [2013]To determine the most effective of four oral treatments for hypoglycemia in children with type 1 diabetes using a weight-based protocol during diabetes camp.
The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes. [2013]There is a lack of evidence regarding the most effective treatment option for managing naturally occurring hypoglycemia in children with type 1 diabetes. The objectives of this study were (i) to determine if sucrose and fructose are equally effective as glucose in the treatment of spontaneous hypoglycemia in children with type 1 diabetes; and (ii) to determine prestudy and poststudy hypoglycemia treatment preferences.
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. [2022]To determine the effect of a low carbohydrate diet and standard carbohydrate counting on glycaemic control, glucose excursions and daily insulin use compared with standard carbohydrate counting in participants with type 1 diabetes.
Mini-doses of glucagon to prevent hypoglycemia in children with type 1 diabetes refusing food: a case series. [2020]Hypoglycemia in small children with type 1 diabetes is difficult to manage if nausea, vomit or food refusal occurs. If oral carbohydrate cannot be used, there is a hypothetical risk of severe hypoglycemia. The present article describes the effect on glucose of small doses of subcutaneous glucagon to revert hypoglycemia and prevent severe events in small children with type 1 diabetes using a continuous glucose monitoring.
Meal composition is a determinant of lispro-induced hypoglycemia in IDDM. [2019]Lispro is a newly FDA-approved analog of human insulin that will be widely used in patients with IDDM. This insulin, however, may have an increased potential for hypoglycemia because of its very rapid subcutaneous absorption, especially in a setting of decreased carbohydrate intake. Using a short-term prospective randomized parallel group-study design, we studied the incidence of hypoglycemia when lispro was given before breakfast compared with regular human insulin. Since carbohydrate intake is a determinant of postprandial glycemia, we administered three isocaloric meals characterized by low, average, and high carbohydrate content.
Dasiglucagon-A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical Trial. [2022]To evaluate the efficacy and safety of dasiglucagon, a ready-to-use, next-generation glucagon analog in aqueous formulation for subcutaneous dosing, for treatment of severe hypoglycemia in adults with type 1 diabetes.
Intranasal Glucagon: A New Way to Treat Hypoglycemic Emergencies. [2020]Objective: To review the safety, efficacy, and administration of intranasal (IN) glucagon for the management of hypoglycemia. Data Source: A literature search of PubMed/MEDLINE (1995 to November 2019) using the terms intranasal glucagon, nasal glucagon, glucagon, hypoglycemia treatment, and hypoglycemia management was completed. Study Selection and Data Extraction: English-language studies evaluating IN glucagon were evaluated. Data Synthesis: IN glucagon is a newly approved product for the treatment of hypoglycemia in patients with diabetes, 4 years and older. Administered as a 3-mg dose, it was shown to be noninferior to intramuscular (IM) glucagon. In comparison trials, more than 98% of hypoglycemic events were treated successfully with IN glucagon in both pediatric and adult patients. In simulated and real-world studies, IN glucagon was administered in less than a minute for the majority of scenarios. IM glucagon took longer to administer, ranging from 1 to 4 minutes, and often, patients did not receive the intended full dose. Nausea and vomiting, known adverse events for glucagon, as well as local adverse events were most commonly reported with IN glucagon. Relevance to Patient Care and Clinical Practice: IN glucagon is safe, effective, easy to use, and does not require reconstitution prior to use, which can lead to faster delivery in a severe hypoglycemic event. It does not require age- or weight-based dosing. This delivery method offers an option for someone who fears needles or is uncomfortable with injections. Conclusion: IN glucagon is a safe, effective, easy to use, needle-free treatment option for severe hypoglycemia.
Efficacy and Usability of Intranasal Glucagon for the Management of Hypoglycemia in Patients With Diabetes: A Systematic Review. [2021]Hypoglycemia is a common and sometimes life-threatening adverse event associated with insulin, sulfonylurea, and meglitinide therapies. In patients who are disoriented or unconscious, treatment with injectable glucagon is recommended, along with a call for emergency medical assistance. However, limitations of this formulation include difficulty with reconstitution and an unwillingness to administer an injection. In July 2019, intranasal glucagon was approved for use in the acute treatment of severe hypoglycemia in patients ≥4 years of age with diabetes. The purpose of this systematic review was to describe the efficacy, usability, and tolerability of intranasal glucagon 3 mg in patients with diabetes.
Efficacy of Treatment of Nonsevere Hypoglycemia in Adults With Type 1 Diabetes Using Oral Carbohydrates During Automated Insulin Delivery With and Without Glucagon. [2023]Self-management guidelines for nonsevere hypoglycemia (NS-H) in type 1 diabetes recommend 15 g of simple carbohydrates (CHO) at 15-minute intervals. Because automated insulin delivery (AID) preventively reduces or suspends insulin infusion for imminent hypoglycemia, we aimed to determine whether guidelines were excessive during AID.
Optimal Carbohydrate Dose for Treatment of Nonsevere Hypoglycemia in Insulin-Treated Patients With Diabetes: A Narrative Review. [2022]Nonsevere hypoglycemia in people with diabetes is usually treated with rapid-acting carbohydrate, of which glucose is the most suitable form. A quantity of 15 g is recommended and repeated after 15 min if hypoglycemia persists. This recommendation has not changed for several years despite the introduction of continuous glucose monitoring, newer and more flexible insulin regimens and improved insulin delivery. The present review has examined published studies that have explored how effectively defined amounts of carbohydrate treat nonsevere hypoglycemia in adults with insulin-treated diabetes. For most nonsevere episodes of hypoglycemia, the optimal treatment is 15 to 20 g of oral glucose. However, this dose may not be appropriate with many current insulins and insulin pump therapy, where doses of glucose may have to be individualized, and based on body weight or the type of insulin delivery system. Current guidelines on hypoglycemia treatment for newer glucose-lowering therapies may require re-evaluation.
Glycerol Potentiates the Effects of Glucose in Promoting Glucose Recovery During Hypoglycemia: From Basic to Clinical Investigations and Their Therapeutic Application. [2021]We compared the effect of oral glucose versus oral glucose combined with glycerol (glucose + glycerol) in promoting glucose recovery during hypoglycemia. These studies were carried out in two series of experiments. In the first series of experiments, 16 overnight fasted rats received an intraperitoneal injection of lispro insulin (1 IU/kg), and 25 min later, they received oral water (control), glucose (0.25 g/kg), glycerol (2.5 g/kg), or glucose (0.25 g/kg) + glycerol (2.5 g/kg). In the second series of experiments on 164 eligible type 1 diabetic (T1D) patients, 30 individuals with a history of hypoglycemia were recruited. Five volunteers did not meet the inclusion criteria and two subjects were excluded after starting the clinical investigation; 23 patients concluded the study. All patients with symptoms of hypoglycemia ingested oral glucose (15 g) or glucose (15 g) + glycerol (9.45 g). To treat hypoglycemia in T1D patients, preparations containing glucose alone or glucose + glycerol were used alternately (2 weeks/2 weeks) in a double-blind crossover scheme. Throughout the clinical research (4 weeks), glucose concentrations were assessed with a continuous glucose monitoring device and the results after the use of glucose alone or glucose + glycerol preparations were compared. Oral glucose combined with glycerol was more effective in promoting glucose recovery in comparison with glucose alone, not only in rats but also in T1D patients. Taken together, our experimental and clinical investigations reported the best performance of oral administration of glucose + glycerol in comparison with isolated glucose.
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. [2021]Recommended hypoglycemia treatment in adults with T1D consists of 15 g of rapid absorption carbohydrates. We aimed to evaluate the response to fewer carbohydrates for treating hypoglycemia in patients with T1D on insulin pumps with predictive suspension technology (PLGS).