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Carvedilol in Treating Hypoglycemia Unawareness

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03538015
Recruitment Status : Terminated (Sponsor was impacted by COVID-19 and did not have sufficient funds to continue.)
First Posted : May 25, 2018
Results First Posted : September 9, 2020
Last Update Posted : September 9, 2020
Sponsor:
Information provided by (Responsible Party):
Owen Chan, PhD, University of Utah

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.


Condition or disease Intervention/treatment Phase
Hypoglycemia Unawareness Drug: Carvedilol 3.125 mg Drug: Carvedilol 2.5 mg Drug: Placebo capsule Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blinded, randomized, placebo-controlled study in patients with Type 1 diabetes mellitus and hypoglycemia unawareness
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: The Use of Low-Dose Carvedilol to Improve Hypoglycemia Awareness in Patients With Type 1 Diabetes Mellitus
Actual Study Start Date : April 22, 2019
Actual Primary Completion Date : August 10, 2020
Actual Study Completion Date : August 10, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypoglycemia
Drug Information available for: Carvedilol

Arm Intervention/treatment
Experimental: Carvedilol 3.125 mg
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
Participants will receive a 3.125 mg oral dose of carvedilol twice daily during the 4-week treatment period
Other Name: Coreg

Experimental: Carvedilol 2.5 mg
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
Participants will receive a 2.5 mg oral dose of carvedilol twice daily during the 4-week treatment period
Other Name: Coreg

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




Primary Outcome Measures :
  1. Change in Hypoglycemia Symptom Score [ Time Frame: Baseline and 4 Weeks ]
    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.


Secondary Outcome Measures :
  1. Change in Blood Glucagon [ Time Frame: Baseline and 4 Weeks ]
    Blood samples will be drawn from study participants at baseline and after the 4-week treatment period during the clamp procedure. The average change in blood glucagon level will be compared between the carvedilol and placebo groups.

  2. Change in Blood Epinephrine [ Time Frame: Baseline and 4 Weeks ]
    Blood samples will be drawn from study participants at baseline and after the 4-week treatment period during the clamp procedure. The average change in blood epinephrine level will be compared between the carvedilol and placebo groups.

  3. Change in Blood Norepinephrine [ Time Frame: Baseline and 4 Weeks ]
    Blood samples will be drawn from study participants at baseline and after the 4-week treatment period during the clamp procedure. The average change in blood norepinephrine level will be compared between the carvedilol and placebo groups.

  4. Change in Blood Cortisol [ Time Frame: Baseline and 4 Weeks ]
    Blood samples will be drawn from study participants at baseline and after the 4-week treatment period during the clamp procedure. The average change in blood cortisol level will be compared between the carvedilol and placebo groups.

  5. Change in Blood Growth Hormone [ Time Frame: Baseline and 4 Weeks ]
    Blood samples will be drawn from study participants at baseline and after the 4-week treatment period during the clamp procedure. The average change in blood growth hormone level will be compared between the carvedilol and placebo groups.

  6. Frequency of CGM-Determined Hypoglycemic Episodes [ Time Frame: 5 Weeks ]
    The number of hypoglycemic episodes as determined by CGM will be determined during the 4-week treatment period and compared to the 1-week pre-study baseline period.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03538015


Locations
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United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Owen Chan, PhD
Investigators
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Principal Investigator: Owen Chan, Ph.D. University of Utah
  Study Documents (Full-Text)

Documents provided by Owen Chan, PhD, University of Utah:
Informed Consent Form  [PDF] September 19, 2019

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Responsible Party: Owen Chan, PhD, Associate Professor of Medicine, University of Utah
ClinicalTrials.gov Identifier: NCT03538015    
Other Study ID Numbers: IRB #108879
First Posted: May 25, 2018    Key Record Dates
Results First Posted: September 9, 2020
Last Update Posted: September 9, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Owen Chan, PhD, University of Utah:
Type 1 Diabetes Mellitus
β-blocker
Additional relevant MeSH terms:
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Unconsciousness
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Carvedilol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Antioxidants
Protective Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists