Safety and Efficacy of Tirzepatide (Spartina) in Obese Kidney Transplant Recipients: A Pilot Study on Weight Loss, Gastrointestinal Tolerability, and Graft Function
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Percent Change in Body Weight From Baseline at Week 24
研究概览
简要总结
Post-transplant obesity is a common complication after kidney transplantation, largely attributed to recovery from uremia, increased appetite, sedentary lifestyle, and long-term corticosteroid exposure. Obesity in kidney transplant recipients increases the risk of cardiovascular disease, post-transplant diabetes mellitus (PTDM), and may contribute to graft injury through hyperfiltration-related mechanisms, potentially leading to reduced graft survival. Current approaches for weight management in transplant recipients, including lifestyle modification, are often insufficient, while bariatric surgery carries considerable risks and concerns regarding altered absorption of immunosuppressive medications.
Tirzepatide (Iranian brand name: Spartina), the first dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated superior effects on weight reduction and glycemic control compared with earlier GLP-1 receptor agonists in the general population. However, its use in kidney transplant recipients requires careful evaluation due to potential gastrointestinal adverse effects, dehydration risk, and possible interaction with calcineurin inhibitor absorption caused by delayed gastric emptying.
This prospective single-arm pilot clinical trial aims to assess the preliminary safety and efficacy of tirzepatide in obese kidney transplant recipients with stable graft function. Outcomes include changes in anthropometric indices, percent weight change, gastrointestinal tolerability, immunosuppressive drug trough levels, and graft function over 24 weeks of treatment.
详细描述
Obesity following kidney transplantation is a frequent metabolic complication, related to improved appetite after resolution of uremia, reduced physical activity, and corticosteroid therapy. Post-transplant obesity is associated with increased risk of cardiovascular disease, PTDM, and chronic graft dysfunction. In addition, obesity-related hyperfiltration may accelerate structural injury to the transplanted kidney, potentially contributing to glomerulopathy and reduced graft survival.
Pharmacologic management of obesity in kidney transplant recipients remains challenging. Lifestyle-based interventions often fail to produce sustained weight loss. Bariatric surgery may be effective but is associated with increased risks in transplant recipients, including adhesions, infection, and altered absorption of immunosuppressive agents.
Tirzepatide is a dual GIP and GLP-1 receptor agonist with robust effects on weight reduction and glycemic control. Nevertheless, its safety profile in kidney transplant recipients remains insufficiently studied, particularly regarding gastrointestinal adverse events, dehydration risk, and the potential impact on immunosuppressive drug exposure due to delayed gastric emptying.
This study is designed as a prospective single-arm pilot clinical trial. Eligible kidney transplant recipients with obesity and stable graft function will receive weekly subcutaneous tirzepatide for 24 weeks using a stepwise dose escalation regimen. Participants will be monitored for changes in body weight, BMI, waist circumference, graft function parameters (serum creatinine and eGFR), metabolic indices (fasting glucose, HbA1c, lipid profile), gastrointestinal adverse events, and calcineurin inhibitor trough levels (tacrolimus or cyclosporine).
This pilot trial will provide preliminary evidence regarding feasibility, safety, and potential efficacy of tirzepatide in this high-risk transplant population and may guide the design of larger randomized controlled trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Kidney transplant recipient with ≥12 months since transplantation
- •BMI ≥ 27 kg/m²
- •Stable graft function in the last 3 months (serum creatinine variation < 20%)
- •Stable immunosuppressive regimen
- •Ability to provide written informed consent
排除标准
- •History of pancreatitis
- •Severe gastroparesis
- •History of medullary thyroid carcinoma (MTC) or MEN2 syndrome
- •eGFR < 30 mL/min/1.73m²
- •Acute rejection episode within the past 6 months
- •Any condition judged by the investigator to interfere with study participation or safety
研究组 & 干预措施
Tirzepatide(Spartina)
Route: Subcutaneous injection (SC)
- Frequency: Once weekly
- Duration: 24 weeks
- Dose escalation:
- Weeks 1-4: 2.5 mg weekly
- Weeks 5-8: 5 mg weekly (if tolerated)
- Weeks 9-24: Continue 5 mg weekly or increase to 7.5 mg weekly based on tolerability and physician judgment
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Percent Change in Body Weight From Baseline at Week 24
时间窗: Baseline to Week 24
Percent change in body weight compared to baseline
Incidence of Gastrointestinal Adverse Events
时间窗: Baseline to Week 24 (monthly assessment)
Number of participants with gastrointestinal adverse events ( nausea, vomiting, diarrhea, constipation, abdominal pain) graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Change in Serum Creatinine
时间窗: Baseline to Week 24
Change from baseline in serum creatinine (mg/dl).
次要结局
- Change in Body Mass Index (BMI)(Baseline to Week 24)
- Change in Waist Circumference(Baseline to Week 24)
- Proportion of Participants Achieving Clinically Meaningful Weight Loss • Definition(week 24)
- change in tacrolimus trough Level(Monthly monitoring through Week 24)
- Change in Fasting blood glucose(Baseline to Week 24)
- Change in systolic blood pressure(Baseline to Week 24)
- Change in Proteinuria(Baseline to Week 24)
- Change in diastolic blood pressure(Baseline to week 24)
研究者
nooshin dalili
Associate Professor of Nephrology
Shahid Beheshti University of Medical Sciences