The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes

NCT02660242 | Completed Phase 2 Results

• 1 other identifier: T1DX Mini-dose Exercise
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

This project focuses on development of new strategy for the prevention of exercise-associated hypoglycemia using mini-dose glucagon.

Conditions

Diabetes Mellitus, Type 1

Keywords

T1D; Type 1 Diabetes; Mini-dose Glucagon; Adults; Exercise; Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Glycemic Response During Exercise and Early Recovery

  Comparison of glycemic response (from blood glucose) during exercise and early recovery between each exercise strategy.

  0 to 75 minutes following exercise initiation (0, 5, 10, 15, 25, 35, 45, 50, 55, 60, 75 min)

Secondary Outcomes (11)

• Number of Participants With Hypoglycemia (<70 mg/dL) During Exercise and Early Recovery

  0 to 75 minutes following exercise initiation

• Number of Participants With Hyperglycemia (≥250 mg/dL) During Exercise and Early Recovery

  0 to 75 minutes following exercise initiation

• Continuous Glucose Monitor (CGM) Metrics During Late Recovery - Nadir Glucose

  90 min after the standard meal until 1200 noon the day after each exercise session

• CGM Metrics During Late Recovery - Peak Glucose

  90 min after the standard meal until 1200 noon the day after each exercise session

• CGM Metrics During Late Recovery - Mean Glucose

  90 min after the standard meal until 1200 noon the day after each exercise session

Study Arms (4)

Control

NO INTERVENTION

No basal insulin adjustment, no carbohydrate intake (until glucose drops \<70 mg/dL).

Basal insulin reduction

ACTIVE COMPARATOR

Basal insulin reduction to 50% five minutes before the start of exercise.

Other: Basal Insulin Reduction

Glucose Tabs

ACTIVE COMPARATOR

Dextrose tabs orally (20 grams) five minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).

Other: Glucose Tabs

G-Pen Mini™ (glucagon injection)

EXPERIMENTAL

Glucagon (150 µg) five minutes before the start of exercise (SQ-abdomen).

Drug: G-Pen Mini™ (glucagon injection)

Interventions

G-Pen Mini™ (glucagon injection) DRUG

Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).

Also known as: mini-dose glucagon

G-Pen Mini™ (glucagon injection)

Glucose Tabs OTHER

Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).

Also known as: over-the-counter oral glucose tablets

Glucose Tabs

Basal Insulin Reduction OTHER

Basal insulin reduction to 50% 5 minutes before the start of exercise.

Basal insulin reduction

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin
• Age 18-\<65 years
• Duration of T1D ≥ 2 years
• Random C-peptide \< 0.6 ng/ml
• Using continuous subcutaneous insulin infusion (CSII; insulin pump) for at least 6 months, with no plans to discontinue pump use during the study
• Exercises regularly, i.e. ≥30 minutes moderate or more vigorous aerobic activity X ≥3 times/week
• Body mass index (BMI) \<30 kg/m2
• Females must meet one of the following criteria:
• Of childbearing potential and not currently pregnant or lactating, and agrees to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study; or
• Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
• In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
• Willing to adhere to the protocol requirements for the duration of the study
• Must be enrolled in the T1D Exchange clinic registry or willing to join the registry

You may not qualify if:

• One or more severe hypoglycemic episodes in the past 12 months (as defined by an episode that required third party assistance for treatment)
• Active diabetic retinopathy (proliferative diabetic retinopathy or vitreous hemorrhage in past 6 months) that could potentially be worsened by exercise protocol
• Peripheral neuropathy with insensate feet
• Cardiovascular autonomic neuropathy with inappropriate heart rate response to exercise
• Use of non-insulin anti-diabetic medications
• Use of beta-blockers
• Use of agents that affect hepatic glucose production such as beta adrenergic agonists, xanthine derivatives
• Use of Pramlintide
• Currently following a very low calorie or other weight-loss diet
• Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study or planning to participate in another such study during participation in the current study

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• Xeris Pharmaceuticals: collaborator

Study Sites (2)

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (17)

• Chu L, Hamilton J, Riddell MC. Clinical management of the physically active patient with type 1 diabetes. Phys Sportsmed. 2011 May;39(2):64-77. doi: 10.3810/psm.2011.05.1896.

  PMID: 21673486 BACKGROUND

• West DJ, Morton RD, Bain SC, Stephens JW, Bracken RM. Blood glucose responses to reductions in pre-exercise rapid-acting insulin for 24 h after running in individuals with type 1 diabetes. J Sports Sci. 2010 May;28(7):781-8. doi: 10.1080/02640411003734093.

  PMID: 20496226 BACKGROUND

• Brazeau AS, Rabasa-Lhoret R, Strychar I, Mircescu H. Barriers to physical activity among patients with type 1 diabetes. Diabetes Care. 2008 Nov;31(11):2108-9. doi: 10.2337/dc08-0720. Epub 2008 Aug 8.

  PMID: 18689694 BACKGROUND

• Rabasa-Lhoret R, Bourque J, Ducros F, Chiasson JL. Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus insulin regimen (ultralente-lispro). Diabetes Care. 2001 Apr;24(4):625-30. doi: 10.2337/diacare.24.4.625.

  PMID: 11315820 BACKGROUND

• Campbell MD, Walker M, Trenell MI, Jakovljevic DG, Stevenson EJ, Bracken RM, Bain SC, West DJ. Large pre- and postexercise rapid-acting insulin reductions preserve glycemia and prevent early- but not late-onset hypoglycemia in patients with type 1 diabetes. Diabetes Care. 2013 Aug;36(8):2217-24. doi: 10.2337/dc12-2467. Epub 2013 Mar 20.

  PMID: 23514728 BACKGROUND

• Stenerson M, Cameron F, Payne SR, Payne SL, Ly TT, Wilson DM, Buckingham BA. The impact of accelerometer use in exercise-associated hypoglycemia prevention in type 1 diabetes. J Diabetes Sci Technol. 2015 Jan;9(1):80-5. doi: 10.1177/1932296814551045. Epub 2014 Sep 17.

  PMID: 25231116 BACKGROUND

• Tsalikian E, Mauras N, Beck RW, Tamborlane WV, Janz KF, Chase HP, Wysocki T, Weinzimer SA, Buckingham BA, Kollman C, Xing D, Ruedy KJ; Diabetes Research In Children Network Direcnet Study Group. Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus. J Pediatr. 2005 Oct;147(4):528-34. doi: 10.1016/j.jpeds.2005.04.065.

  PMID: 16227041 BACKGROUND

• Tanenberg RJ, Newton CA, Drake AJ. Confirmation of hypoglycemia in the "dead-in-bed" syndrome, as captured by a retrospective continuous glucose monitoring system. Endocr Pract. 2010 Mar-Apr;16(2):244-8. doi: 10.4158/EP09260.CR.

  PMID: 19833577 BACKGROUND

• Campbell MD, Walker M, Trenell MI, Luzio S, Dunseath G, Tuner D, Bracken RM, Bain SC, Russell M, Stevenson EJ, West DJ. Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial. PLoS One. 2014 May 23;9(5):e97143. doi: 10.1371/journal.pone.0097143. eCollection 2014.

  PMID: 24858952 BACKGROUND

• Taplin CE, Cobry E, Messer L, McFann K, Chase HP, Fiallo-Scharer R. Preventing post-exercise nocturnal hypoglycemia in children with type 1 diabetes. J Pediatr. 2010 Nov;157(5):784-8.e1. doi: 10.1016/j.jpeds.2010.06.004. Epub 2010 Jul 21.

  PMID: 20650471 BACKGROUND

• Riddell MC, Bar-Or O, Ayub BV, Calvert RE, Heigenhauser GJ. Glucose ingestion matched with total carbohydrate utilization attenuates hypoglycemia during exercise in adolescents with IDDM. Int J Sport Nutr. 1999 Mar;9(1):24-34. doi: 10.1123/ijsn.9.1.24.

  PMID: 10036339 BACKGROUND

• Robertson K, Riddell MC, Guinhouya BC, Adolfsson P, Hanas R; International Society for Pediatric and Adolescent Diabetes. ISPAD Clinical Practice Consensus Guidelines 2014. Exercise in children and adolescents with diabetes. Pediatr Diabetes. 2014 Sep;15 Suppl 20:203-23. doi: 10.1111/pedi.12176. No abstract available.

  PMID: 25182315 BACKGROUND

• Camacho RC, Galassetti P, Davis SN, Wasserman DH. Glucoregulation during and after exercise in health and insulin-dependent diabetes. Exerc Sport Sci Rev. 2005 Jan;33(1):17-23.

  PMID: 15640716 BACKGROUND

• Oskarsson PR, Lins PE, Wallberg Henriksson H, Adamson UC. Metabolic and hormonal responses to exercise in type 1 diabetic patients during continuous subcutaneous, as compared to continuous intraperitoneal, insulin infusion. Diabetes Metab. 1999 Dec;25(6):491-7.

  PMID: 10633873 BACKGROUND

• Haymond MW, Schreiner B. Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes. Diabetes Care. 2001 Apr;24(4):643-5. doi: 10.2337/diacare.24.4.643.

  PMID: 11315823 BACKGROUND

• Diabetes Research in Children Network (DirecNet) Study Group; Tsalikian E, Kollman C, Tamborlane WB, Beck RW, Fiallo-Scharer R, Fox L, Janz KF, Ruedy KJ, Wilson D, Xing D, Weinzimer SA. Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin. Diabetes Care. 2006 Oct;29(10):2200-4. doi: 10.2337/dc06-0495.

  PMID: 17003293 BACKGROUND

• Rickels MR, DuBose SN, Toschi E, Beck RW, Verdejo AS, Wolpert H, Cummins MJ, Newswanger B, Riddell MC; T1D Exchange Mini-Dose Glucagon Exercise Study Group. Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2018 Sep;41(9):1909-1916. doi: 10.2337/dc18-0051. Epub 2018 May 18.

  PMID: 29776987 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Motor Activity; Hypoglycemia

Interventions

Glucagon

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Stephanie DuBose
• Organization: Jaeb Center for Health Research

sdubose@jaeb.org

813.975.8690

Study Officials

• Michael Riddell, PhD

  York University

  STUDY CHAIR

• Michael Rickels, M.D., M.S.

  University of Pennsylvania

  STUDY CHAIR

• Howard Wolpert, M.D.

  Joslin Diabetes Center

  STUDY CHAIR

• Stephanie DuBose, M.P.H

  Jaeb Center for Health Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 21, 2016
• Study Start: January 1, 2016
• Primary Completion: February 15, 2017
• Study Completion: February 15, 2017
• Last Updated: March 3, 2020
• Results First Posted: August 7, 2018

Record last verified: 2020-02

Locations

US (2)