Calcium Channel Blocker in Myotonic Dystrophy Type 1 (CAP DM1)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 主要终点
- Number of Subjects Who Provided Informed Consent
研究概览
简要总结
This is a Phase 1 clinical trial designed to evaluate the safety and tolerability of amlodipine, a calcium channel blocker, in adults with Myotonic Dystrophy Type 1 (DM1). Amlodipine is being studied to see if it can improve muscle strength, reduce stiffness (myotonia), and improve function by modifying calcium flow in muscle cells. All participants will receive amlodipine starting at 2.5 mg daily for 2 weeks, then 5 mg for 4 weeks. After that, participants will be randomly assigned to continue on 5 mg or increase to 10 mg for an additional 4 weeks. The main goals are to assess changes in blood pressure and any adverse events to determine whether the drug is safe in this population. The study will also explore how amlodipine affects muscle strength, mobility, fatigue, and daily function using clinical tests and questionnaires. Findings will inform a future phase 2 trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or Female between the ages 18 and 65, inclusive.
- •A genetically confirmed diagnosis of DM1, having a repeat expansion in the DMPK gene with at least 100 CTG repeats.
- •Grip strength less than 50% predicted based on age, height, and sex.
- •Video hand opening time is 4 sec or greater for at least one hand.
- •Ambulatory and able to walk 10 meters.
- •Willingness to discontinue anti-myotonia drugs at least 2 weeks prior to screening.
- •Highly effective method of contraception in women with childbearing potential.
排除标准
- •Congenital DM1 as defined by symptom onset in the first 4 weeks of life.
- •Abnormal liver function tests (LFTs): alanine aminotransferase (ALT), or aspartate aminotransferase (AST) >3 x upper limit of normal. Total bilirubin > 1.5 mg/dL, or INR > 1.3, or evidence of current active or chronic infection with hepatitis C, hepatitis B or other hepatobiliary conditions other than DM1 (or attributed to DM1) that cause abnormal liver laboratory parameters (e.g., hemochromatosis, Wilson's disease, autoimmune hepatitis)
- •Current or recent infection requiring antibiotic treatment within 2 weeks prior to screening.
- •Abnormal vital signs, including systolic blood pressure < 90 mmHg and diastolic blood pressure < 60 mmHg.
- •Treatment with concomitant medications with potential interactions with amlodipine, these may include but are not limited to sildenafil, cyclosporin, atorvastatin at high dosages (80 mg daily), simvastatin (at dosages higher than 20 mg daily) or strong inhibitors of CYP3A
- •A history of syncope.
- •A history of symptomatic hypotension.
- •Initiation or change in doses of concomitant medications, including herbal supplements, if in the opinion of the Investigator, may impact the results of the study.
- •Women of childbearing potential must have a negative pregnancy test, cannot be planning a pregnancy, and cannot be breastfeeding at any time during the study.
- •Known history of substance and/or alcohol abuse within one year prior to screening.
- •The presence of comorbidities that, in the opinion of the Investigator, may influence study results, including, but not limited to, uncontrolled diabetes, generalized or mononeuropathy of the upper extremities, or cervical radiculopathy resulting in weakness and atrophy.
- •Concurrent treatment with calcium channel blocker.
- •Known ischemic or non-ischemic moderate or severe heart failure as defined by symptoms suggestive of heart failure or reduced left ventricular ejection fraction (LVEF) on echocardiogram < 55%.
- •Moderate or severe aortic stenosis or other obstruction of the left ventricle outflow tract.
- •Known sensitivity or allergy to amlodipine.
研究组 & 干预措施
Cohort A
Amlodipine 5 mg
干预措施: Amlodipine (Drug)
Cohort B
Amlodipine 10 mg
干预措施: Amlodipine (Drug)
结局指标
主要结局
Number of Subjects Who Provided Informed Consent
时间窗: Baseline
The total number of participants who signed the informed consent document and were enrolled in the study.
Number of Completed Study Visits
时间窗: Baseline to End of Study at week 10
The total number of completed study visits, averaged across all enrolled participants. A visit is considered completed if all required procedures for that visit were performed.
Number of Subjects Who Completed the Study Without Drug Discontinuation
时间窗: Baseline to End of Study at week 10
Number of participants who completed all study visits and remained on study drug throughout the study period without permanent discontinuation due to adverse events, withdrawal, or protocol deviations.
Number of Subjects Who Completed the Study
时间窗: Baseline to End of Study at week 10
Number of participants who completed all required study visits and procedures through the final study visit.
次要结局
- Mean Change in Systolic Blood Pressure(Baseline to End of Study at week 10)
- Number of Participants With Non-Serious Adverse Events(Baseline to End of Study at week 10)
研究者
Johanna Hamel
Associate Professor - Department of Neurology, NMD (SMD)
University of Rochester