Amitriptyline in Treating Hypoglycemia

NCT ID: NCT03591458

Last Updated: 2019-07-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-01
• Study Completion Date: 2019-06-03

Brief Summary

Patients with type 1 diabetes mellitus (T1DM) commonly experience hypoglycemia and develop impaired awareness of hypoglycemia. Many patients using continuous glucose monitoring (CGM) system to mitigate these complications, but continue to spend a significant amount of time in hypoglycemia. The long-term goal is to develop novel and readily available therapeutic approaches to improve hypoglycemia course and awareness in T1DM patients. The objective of this study is to determine whether amitriptyline will improve hypoglycemia course and the ability to recognize hypoglycemic events in T1DM patients who are using CGM.

Detailed Description

Poorly controlled T1DM can lead to serious and devastating complications, including microvascular (retinopathy, neuropathy and nephropathy) and cardiovascular disease. Both diabetic microvascular and cardiovascular complications can be reduced by intensive insulin therapy and strict blood glucose aiming for hemoglobin A1C (HbA1c) less or equal to 7%. However, a tighter glycemic control correlates with a higher incidence of hypoglycemia and severe hypoglycemia. As well, recurrent episodes of hypoglycemia reduce patients' ability to recognize hypoglycemic episodes (a condition termed impaired awareness of hypoglycemia). Impaired awareness of hypoglycemia is also associated with an increased risk of severe hypoglycemia. Severe hypoglycemia can lead to seizures, emergency room visits/hospitalization, fear of hypoglycemia, compromised quality of life and potentially death. Thus, hypoglycemia and impaired awareness of hypoglycemia are major barriers to optimal glycemic control.

Real-time continuous glucose monitoring (rtCGM) is a technique which measures interstitial glucose levels every five minutes to estimate coincidental blood glucose levels. A rtCGM will alert patients of hyper/hypoglycemic events at seg glucose thresholds and when the blood glucose levels are rapidly rising/declining. However, many patients using rtCGM continue to have impaired awareness of hypoglycemia and spend a significant amount of time in hypoglycemia.

In an animal model, amitriptyline, a tricyclic antidepressant, demonstrated its ability to completely restore hypoglycemia awareness. This potential effect of amitriptyline on human, however, has not been tested.

In the current study, amitriptyline will be studied as an adjuvant treatment of rtCGM to further improve hypoglycemia course and T1DM patients' ability to recognize hypoglycemic episode.

Conditions

Type1 Diabetes Mellitus; Hypoglycemia Unawareness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amitriptyline

Participants will be initiated on 25 mg Amitriptyline daily for two weeks during the Titration Period. Amitriptyline dose will be increased to 50 mg daily for 8 weeks during the Intervention Period. Finally, the dose of Amitriptyline will be reduced to 25 mg daily during the two week Taper Period.

Group Type: EXPERIMENTAL

Amitriptyline

Intervention Type: DRUG

Participants will receive a supply of Amitriptyline capsules for titration, intervention, and taper periods.

Placebo

Participants will be initiated on a daily Placebo capsule matching the 25 mg Amitriptyline during the Titration Period. The daily dose will be changed to the Placebo capsule matching the 50 mg Amitriptyline for 8 weeks during the Intervention Period. Finally, the daily dose will be changed back to the Placebo capsule matching the 25 mg Amitriptyline during the two week Taper period.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive a supply of Placebo capsules, matching those of Amitriptyline, for the titration, intervention, and taper periods

Interventions

Amitriptyline

Participants will receive a supply of Amitriptyline capsules for titration, intervention, and taper periods.

Intervention Type: DRUG

Placebo

Participants will receive a supply of Placebo capsules, matching those of Amitriptyline, for the titration, intervention, and taper periods

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects with Type 1 Diabetes Mellitus for at least 5 years or more
• Age between 21 to 60 years old
• HbA1c less or equal to 9% with the latest measurement within the last 3 months
• Use of real time Continuous Glucose Monitoring (rtCGM) providing continuous glucose data points for at least 3 months, and at least 80% of CGM readings available over the last 2-week period
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines

Exclusion Criteria

• Ongoing or recent history of major depressive disorder, or other ongoing major psychiatric disorders
• History of anti-depressant use within the last three months
• Insulin pump linked to a CGM with programmed automatic insulin adjustment or suspension
• History of advanced cardiac, liver, kidney or neurological disease
• Active malignancy
• Uncontrolled Human Immunodeficiency Virus diseases
• Advanced diabetic retinopathy, neuropathy, or nephropathy
• Frequent acetaminophen use which can disrupt CGM accuracy
• Pregnancy or female of child-bearing potential unable to practice effective contraception during the study period
• Breastfeeding female, or female with prospective plan to initiate breastfeeding
• Ongoing history of alcohol abuse
• Contraindication to amitriptyline use, including hypersensitivity to amitriptyline or any component of the formulation, co-administration with or within 14 days of Monoamine Oxidase Inhibitors and co-administration with cisapride
• Inability to understand or cooperate with study procedures, including taking study drugs and recording hypoglycemic symptoms.

• < 80% of CGM readings available over the last 2-week period
• Time spent in hypoglycemia (i.e., < 70 mg/dL) for < 5% over a 2-week period on based on CGM reading.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yu Kuei Lin, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Utah

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

IRB_00110853

Identifier Type: -

Identifier Source: org_study_id