Carvedilol in Treating Hypoglycemia Unawareness

NCT03538015 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: IRB #108879
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes mellitus (T1DM) can lead to cardiovascular, renal and neurological complications if left poorly-controlled over prolonged periods of time. However, lowering glycemic goals for diabetic patients increases their risk for hypoglycemia exposure. Hypoglycemia is associated with symptoms such as heart palpitations, fatigue, shakiness, anxiety, confusion, and blurred vision. Recurrent hypoglycemia leads to impairment of the body's autonomic and symptomatic responses to this condition, and can result in loss of awareness in the patient of the hypoglycemic state. Repeated incidences of hypoglycemia from loss of this awareness can result in even more hypoglycemic episodes and more severe outcomes, such as loss of consciousness, accidents, hospitalization and even death if left untreated. The aim of this study is to investigate whether adrenergic blockade through the use of low-dose carvedilol treatment can improve hypoglycemia awareness and the counterregulatory hormone responses to hypoglycemia in T1DM patients with impaired awareness of hypoglycemia.

Conditions

Hypoglycemia Unawareness

Keywords

Type 1 Diabetes Mellitus; β-blocker

Outcome Measures

Primary Outcomes (1)

• Change in Hypoglycemia Symptom Score

  Participants will complete the Edinburgh Hypoglycemia Symptom questionnaire at baseline and after the 4-week treatment period. The average change in hypoglycemia symptom score will be compared between the carvedilol and placebo groups.

  Baseline and 4 Weeks

Secondary Outcomes (6)

• Change in Blood Glucagon

  Baseline and 4 Weeks

• Change in Blood Epinephrine

  Baseline and 4 Weeks

• Change in Blood Norepinephrine

  Baseline and 4 Weeks

• Change in Blood Cortisol

  Baseline and 4 Weeks

• Change in Blood Growth Hormone

  Baseline and 4 Weeks

Study Arms (3)

Carvedilol 3.125 mg

EXPERIMENTAL

After enrollment, participants will be placed on continuous glucose monitoring (CGM). One week after CGM placement, participants will undergo the first hypoglycemic clamp study to obtain baseline measures of hypoglycemia frequency, hypoglycemia awareness scores and hormone responses. Following the initial clamp procedure, participants will receive 4 weeks of low-dose carvedilol treatment. After 4 weeks of treatment, the participants will undergo a second hypoglycemic clamp session.

Drug: Carvedilol 3.125 mg

Carvedilol 2.5 mg

EXPERIMENTAL

After enrollment, participants will be placed on continuous glucose monitoring (CGM). One week after CGM placement, participants will undergo the first hypoglycemic clamp study to obtain baseline measures of hypoglycemia frequency, hypoglycemia awareness scores and hormone responses. Following the initial clamp procedure, participants will receive 4 weeks of low-dose carvedilol treatment. After 4 weeks of treatment, the participants will undergo a second hypoglycemic clamp session.

Drug: Carvedilol 2.5 mg

Placebo capsule

PLACEBO COMPARATOR

After enrollment, participants will be placed on continuous glucose monitoring (CGM). One week after CGM placement, participants will undergo the first hypoglycemic clamp study to obtain baseline measures of hypoglycemia frequency, hypoglycemia awareness scores and hormone responses. Following the initial clamp procedure, participants will receive 4 weeks of placebo treatment. After 4 weeks of treatment, the participants will undergo a second hypoglycemic clamp session.

Drug: Placebo capsule

Interventions

Carvedilol 3.125 mg DRUG

Participants will receive a 3.125 mg oral dose of carvedilol twice daily during the 4-week treatment period

Also known as: Coreg

Carvedilol 3.125 mg

Carvedilol 2.5 mg DRUG

Participants will receive a 2.5 mg oral dose of carvedilol twice daily during the 4-week treatment period

Also known as: Coreg

Carvedilol 2.5 mg

Placebo capsule DRUG

Participants will receive a matching oral dose of placebo capsule twice daily during the 4-week treatment period

Placebo capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of Type 1 diabetes mellitus for more than 5 years
• Age \> 18 years
• Presence of impaired hypoglycemia awareness/unawareness
• Intensive insulin treatment as defined by multiple daily insulin injections (3 or more) or insulin pump therapy
• Negative pregnancy test
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

You may not qualify if:

• Major medical disorders (including liver disease, cardiovascular disease, kidney disease, chronic obstructive pulmonary disease, asthma, active malignancy or HIV)
• Overt diabetes complications (neuropathy, nephropathy, retinopathy)
• Presence of anemia
• Current or recent use of beta-blocker therapy
• Use of diuretics
• Allergies or contraindications to beta-blockers or heparin
• Use of benzodiazepines
• Alcohol, drug or medication abuse
• Frequent use of acetaminophen

Sponsors & Collaborators

• Owen Chan, PhD: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Dr. Owen Chan
• Organization: University of Utah

ochan@u2m2.utah.edu

801-581-7755

Study Officials

• Owen Chan, Ph.D.

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Double-blinded, randomized, placebo-controlled study in patients with Type 1 diabetes mellitus and hypoglycemia unawareness

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: May 25, 2018
• Study Start: April 22, 2019
• Primary Completion: August 10, 2020
• Study Completion: August 10, 2020
• Last Updated: November 25, 2020
• Results First Posted: September 9, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)