TArgeting Type 1 Diabetes Using POLyamines (TADPOL): A Randomized, Double-Masked, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of Difluoromethylornithine (DFMO) to Preserve Insulin Production in Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 74
- 试验地点
- 14
- 主要终点
- Clinical efficacy of 1000 mg/m2/day of oral DFMO after 6 months of treatment
研究概览
简要总结
The goal of this clinical trial is to test a drug known as DFMO in people with Type 1 Diabetes (T1D). The main question[s] it aims to answer are:
- Does it reduce stress on the cells that make insulin?
- Does it preserve what is left of the body's insulin production? Participants will take either DFMO or a placebo (looks like DFMO but has no active ingredients) two times a day for about 6 months. Participants will have 6 in person visits and 1 phone visit over a period of 12 months. Visits will include blood draws urine collection and other tests.
详细描述
This study will be a multicenter, double-blind, placebo-controlled, 2:1 random assigned, phase II clinical trial for individuals with recent onset type 1 diabetes. The investigators are conducting a double masked placebo-controlled intention to treat study enrolling persons with new onset T1D with documented continued residual C-peptide production. Within 45 days of screening and a run-in period during which eligibility will be determined and glycemic control optimized, subjects will have a 6-month double-masked treatment period with either DFMO or placebo. After a 6-month wash-out period the durability of effect will be assessed. Subjects will be randomly assigned either 1000mg/m2/day oral DFMO or placebo treatment at a 2:1 ratio.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Participant, Care provider and Investigator blinded
入排标准
- 年龄范围
- 4 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females 4- ≥40 years of age with a clinical diagnosis of T1D
- •T1D clinical diagnosis with insulin start date no more than 100 days prior to the time of randomization
- •Random non-fasting C-peptide level of >0.2 pmol/mL (equivalent to >0.6ng/ml) at screening.
- •Positive for any one of the following diabetes-related autoantibodies (IAA, GAA, IA-2, or ZnT8)
- •Treatment naïve of any immunomodulatory agent
- •Normal hearing at screening, defined as acceptable results of pure-tone audiometry (<20 decibel [dB] baseline thresholds for all frequencies tested
排除标准
- •Presence of severe, active disease that interferes with dietary intake or requires the use of chronic medication, with the exception of well-controlled hypothyroidism and mild asthma not requiring oral steroids. Presence of any psychiatric disorder that will affect ability to participate in study.
- •Diabetes other than T1D
- •Chronic illness known to affect glucose metabolism (e.g. Cushing syndrome, polycystic ovarian disorder, cystic fibrosis) or taking medications that affect glucose metabolism (e.g. steroids, metformin)
- •Inability to swallow pills
- •Psychiatric impairment or current use of anti-psychotic medication
- •Any condition that, in the investigator's opinion, may compromise study participation or may confound the interpretation of the study results.
- •Neutropenia (< 1,500 neutrophils/μL)
- •Leukopenia (< 3,000 leukocytes /μL)
- •Lymphopenia ( < 800 lymphocytes/μL)
- •Thrombocytopenia (<100,000 platelets/μL)
- •Clinically significant anemia or Hemoglobin as defined below:
- •In Adults: Hgb <12.0g/dL in females and <13.0g/dL in males In Children: 12- <18: <11.4 g/dL in females and <12.4 g/dL in males In Children: 4- <12: Hgb <11.2 g/dL
- •Impaired renal function (assessed by history and BUN/Creatinine, DFMO is renally excreted)
- •Allergy to milk or soy (components of Boost® drink used for mixed meal tolerance testing)
- •Female participants of child-bearing age with reproductive potential, must not be pregnant and agree to use 2 effective forms of birth control or be abstinent during the study period (see below). Male participants (including men who have had vasectomies) whose partners are pregnant or may be pregnant should use condoms while on study drug, until 2 weeks after discontinuation of drug, while the partner is pregnant.
- •Active seizure disorder, defined as requiring chronic medication at the time of study or having had a seizure within the past 12 months at the time of screening
- •Enrollment into another intervention trial.
- •Use of an automated insulin delivery system, including hybrid closed loop or fully closed loop insulin pumps) that do not allow for manual suspension or temporary modification of insulin delivery for bolus dosing.
研究组 & 干预措施
Treatment Arm
Difluoromethylornithine (DFMO) pill ,1000mg/m2/day, for 6 months
干预措施: DFMO (Drug)
Placebo Arm
Placebo pill taken twice a day orally for 6 months
干预措施: Placebo (Drug)
结局指标
主要结局
Clinical efficacy of 1000 mg/m2/day of oral DFMO after 6 months of treatment
时间窗: 6 month
Primary endpoint defining clinical efficacy will be based on mixed-meal stimulated C-peptide area under the curve (AUC; in arbitrary units) in the treatment group compared to placebo after 6 months of DFMO treatment
Number of participants with treatment-related adverse events as assessed by CTCAE v5
时间窗: through study completion, an average of one year
A summary of serious and non-serious adverse events (AEs) will be reported.
次要结局
- Biomarkers of β cell stress at 3, 6, 9, and 12 months after treatment.(through study completion, an average of one year)
- Clinical efficacy of 1000 mg/m2/day of oral DFMO after 3 months of treatment, 9 months after treatment (or 3 months after treatment end), and 12 months after treatment (or 6 months after treatment end).(through study completion, an average of one year)
- Decrease in urinary polyamides after 6 months of DFMO treatment.(up to 24 weeks after treatment)
研究者
Emily K. Sims
Associate Professor of Pediatrics
Indiana University