Amitriptyline in Treating Hypoglycemia
关键词
抽象
描述
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.
日期
| 最后验证: | 06/30/2019 |
| 首次提交: | 07/07/2018 |
| 提交的预估入学人数: | 07/07/2018 |
| 首次发布: | 07/18/2018 |
| 上次提交的更新: | 07/11/2019 |
| 最近更新发布: | 07/21/2019 |
| 首次提交结果的日期: | 06/05/2019 |
| 首次提交质量检查结果的日期: | 07/11/2019 |
| 首次发布结果的日期: | 07/21/2019 |
| 实际学习开始日期: | 07/31/2018 |
| 预计主要完成日期: | 06/02/2019 |
| 预计完成日期: | 06/02/2019 |
状况或疾病
干预/治疗
Drug: Amitriptyline
Drug: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: 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. | Drug: Amitriptyline Participants will receive a supply of Amitriptyline capsules for titration, intervention, and taper periods. |
| Placebo Comparator: 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. | Drug: Placebo Participants will receive a supply of Placebo capsules, matching those of Amitriptyline, for the titration, intervention, and taper periods |
资格标准
| 有资格学习的年龄 | 21 Years 至 21 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | 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. The participants meeting the above criteria will enter "Run-in Period". At the Visit 2, the following additional exclusion criteria will be applied before study drug randomization: - < 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. |
结果
主要结果指标
1. Glucose Area Under the Curve (AUC): Values < 70 mg/dL [2 Weeks]
2. Glucose Area Under the Curve (AUC): Values < 54 mg/dL [2 Weeks]
3. Ratio of Self-Reported Hypoglycemic Episodes to Total Hypoglycemic Episodes [2 Weeks]
次要成果指标
1. Total Count of Severe Hypoglycemic Episodes [8 Weeks]
2. Hypoglycemia Episode Count With Blood Glucose < 70 mg/dL [2 weeks]
3. Hypoglycemia Episode Count With Blood Glucose < 54 mg/dL [2 weeks]
4. Average Hypoglycemia Duration With Blood Glucose < 70 mg/dL [2 weeks]
5. Average Hypoglycemia Duration With Blood Glucose < 54 mg/dL [2 weeks]
6. Hypoglycemia Awareness Score by Gold Questionnaire [10 Weeks]
7. Hypoglycemia Awareness Score by Clarke Questionnaire [10 Weeks]
8. Hypoglycemia Awareness Score by Pedersen-Bjergaard Questionnaire [10 Weeks]
9. Hypoglycemia Fear Survey Score [10 Weeks]
