Amitriptyline in Treating Hypoglycemia

NCT03591458 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: IRB_00110853
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Type1 Diabetes Mellitus; Hypoglycemia Unawareness

Outcome Measures

Primary Outcomes (3)

• Glucose Area Under the Curve (AUC): Values < 70 mg/dL

  Continuous Glucose Monitoring (CGM) data will be collected for a 2-week period at the end of the Intervention Phase. The mean AUC for glucose values \< 70 mg/dL will be compared between the Amitriptyline and Placebo arms.

  2 Weeks

• Glucose Area Under the Curve (AUC): Values < 54 mg/dL

  Continuous Glucose Monitoring (CGM) data will be collected for a 2-week period at the end of the Intervention Phase. The mean AUC for glucose values \< 54 mg/dL will be compared between the Amitriptyline and Placebo arms.

  2 Weeks

• Ratio of Self-Reported Hypoglycemic Episodes to Total Hypoglycemic Episodes

  Participants will complete a report of all hypoglycemic events experienced during the 2-week surveillance period at the end of the Intervention Phase. The average ratio of self-reported hypoglycemic episodes to total hypoglycemic episodes recorded by Continuous Glucose Monitoring (CGM) will be compared between the Amitriptyline and Placebo arms.

  2 Weeks

Secondary Outcomes (9)

• Total Count of Severe Hypoglycemic Episodes

  8 Weeks

• Hypoglycemia Episode Count With Blood Glucose < 70 mg/dL

  2 weeks

• Hypoglycemia Episode Count With Blood Glucose < 54 mg/dL

  2 weeks

• Average Hypoglycemia Duration With Blood Glucose < 70 mg/dL

  2 weeks

• Average Hypoglycemia Duration With Blood Glucose < 54 mg/dL

  2 weeks

Study Arms (2)

Amitriptyline

EXPERIMENTAL

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.

Drug: Amitriptyline

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Amitriptyline DRUG

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

Amitriptyline

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Interventions

Amitriptyline

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Scott Low
• Organization: University of Utah

scott.low@hsc.utah.edu

801-585-1380

Study Officials

• Yu Kuei Lin, M.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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind, randomized, placebo control

Study Record Dates

• First Submitted: July 8, 2018
• First Posted: July 19, 2018
• Study Start: August 1, 2018
• Primary Completion: June 3, 2019
• Study Completion: June 3, 2019
• Last Updated: July 22, 2019
• Results First Posted: July 22, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)