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

NCT ID: NCT02660242

Last Updated: 2020-03-03

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

16 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-31

Study Completion Date

2017-02-15

Brief Summary

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

Detailed Description

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The primary objective of the protocol is to determine if the administration of mini-dose glucagon administered subcutaneously just before exercise produces better glucose stability than no adjustments for moderate intensity exercise in patients with Type 1 Diabetes (T1D). It will also be assessed whether mini-dose glucagon before exercise produces better glucose stability than basal insulin reductions or extra carbohydrate consumption.

This is a randomized, 4-way crossover trial. The trial will include 16 participants who complete the study.

Each participant will undergo four aerobic exercise sessions (in random order), with different strategies for glucose regulation:

* Control Trial: Fasted exercise, no basal insulin reduction
* Strategy 1: Fasted exercise, basal insulin reduction only (50% reduction in basal rate at 60 minutes before exercise, for the duration of the exercise)
* Strategy 2: Fasted exercise, no basal adjustment + pre-exercise glucose tabs (buccal route-40 grams in total )
* Strategy 3: Fasted exercise, no basal adjustment + pre-exercise mini-dose glucagon (sc)

In all 4 sessions, aerobic exercise will be performed in the fasted state (before a standardized meal) for 45 minuets at \~50-55% of the participant's per-determined aerobic capacity. The participant's pump will be blinded during the control trial, strategy 1, and strategy 3 and an injection of saline will be given during the control trial and strategy 1 so that participant is blinded to strategy.

The primary outcome for this study will be the glycemic response during exercise and early recovery.

Conditions

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Diabetes Mellitus, Type 1

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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Control

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Basal insulin reduction

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

Group Type ACTIVE_COMPARATOR

Basal Insulin Reduction

Intervention Type OTHER

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

Glucose Tabs

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

Group Type ACTIVE_COMPARATOR

Glucose Tabs

Intervention Type OTHER

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

G-Pen Mini™ (glucagon injection)

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

Group Type EXPERIMENTAL

G-Pen Mini™ (glucagon injection)

Intervention Type DRUG

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

Interventions

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G-Pen Mini™ (glucagon injection)

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

Intervention Type DRUG

Glucose Tabs

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

Intervention Type OTHER

Basal Insulin Reduction

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

Intervention Type OTHER

Other Intervention Names

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mini-dose glucagon over-the-counter oral glucose tablets

Eligibility Criteria

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Inclusion Criteria

1. Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin
2. Age 18-\<65 years
3. Duration of T1D ≥ 2 years
4. Random C-peptide \< 0.6 ng/ml
5. Using continuous subcutaneous insulin infusion (CSII; insulin pump) for at least 6 months, with no plans to discontinue pump use during the study
6. Exercises regularly, i.e. ≥30 minutes moderate or more vigorous aerobic activity X ≥3 times/week
7. Body mass index (BMI) \<30 kg/m2
8. 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)
9. 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
10. Willing to adhere to the protocol requirements for the duration of the study
11. Must be enrolled in the T1D Exchange clinic registry or willing to join the registry

Exclusion Criteria

1. One or more severe hypoglycemic episodes in the past 12 months (as defined by an episode that required third party assistance for treatment)
2. Active diabetic retinopathy (proliferative diabetic retinopathy or vitreous hemorrhage in past 6 months) that could potentially be worsened by exercise protocol
3. Peripheral neuropathy with insensate feet
4. Cardiovascular autonomic neuropathy with inappropriate heart rate response to exercise
5. Use of non-insulin anti-diabetic medications
6. Use of beta-blockers
7. Use of agents that affect hepatic glucose production such as beta adrenergic agonists, xanthine derivatives
8. Use of Pramlintide
9. Currently following a very low calorie or other weight-loss diet
10. 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

64 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Xeris Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Riddell, PhD

Role: STUDY_CHAIR

York University

Michael Rickels, M.D., M.S.

Role: STUDY_CHAIR

University of Pennsylvania

Howard Wolpert, M.D.

Role: STUDY_CHAIR

Joslin Diabetes Center

Stephanie DuBose, M.P.H

Role: PRINCIPAL_INVESTIGATOR

Jaeb Center for Health Research

Locations

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Joslin Diabetes Center

Boston, Massachusetts, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 21673486 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20496226 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18689694 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11315820 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23514728 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25231116 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16227041 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19833577 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24858952 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20650471 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10036339 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25182315 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15640716 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10633873 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11315823 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17003293 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29776987 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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T1DX Mini-dose Exercise

Identifier Type: -

Identifier Source: org_study_id

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