Efficacy of Tirzepatide for Weight Management in Patients With Suboptimal Weight Loss After Bariatric Surgery: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 70
- 试验地点
- 3
- 主要终点
- Percentage Change in Body Weight from Baseline to Week 52
研究概览
简要总结
Many people who have bariatric (weight-loss) surgery do not lose as much weight as expected, or they regain weight over time. This study will test whether a medicine called tirzepatide can help these patients lose more weight and improve their overall health.
Participants who had bariatric surgery at least one year ago and still have obesity with insufficient weight loss will be randomly assigned, like a coin flip, to receive either tirzepatide or a placebo (an inactive injection that looks the same). Neither participants nor study staff will know who is receiving which treatment.
Participants will inject the study medicine or placebo once a week for 52 weeks, starting at a low dose that is gradually increased. During the study, researchers will measure body weight, waist size, blood pressure, and blood tests related to metabolism and inflammation. Participants will also answer questionnaires about their quality of life.
The main goal is to find out whether tirzepatide leads to greater weight loss than placebo after one year of treatment.
详细描述
TirBaS is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial evaluating the efficacy of tirzepatide, a dual GIP/GLP-1 receptor agonist, for weight management in adults with a history of bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) performed at least 12 months prior to enrollment, who present with suboptimal weight loss or weight regain.
A total of 70 participants will be randomized in a 1:1 ratio to receive either tirzepatide or matching placebo, administered once weekly by subcutaneous injection. Randomization will be stratified by type of bariatric surgery, baseline BMI category, and time since surgery. Tirzepatide will be up-titrated in 2.5 mg increments every 4 weeks, up to a maximum of 15 mg or the maximum tolerated dose, with weekly dosing continuing through week 52 of the 52-week treatment period.
The primary objective is to assess the effect of tirzepatide versus placebo on the percentage change in body weight from baseline to week 52. Secondary objectives include evaluating changes in cardiometabolic parameters (body weight, BMI, waist circumference, blood pressure, HbA1c, fasting glucose, lipid profile, kidney function, liver profile), inflammatory status (hs-CRP), the proportion of participants achieving clinically meaningful weight loss thresholds (≥5%, ≥10%, ≥15%, ≥20%), and quality of life, assessed using the IWQOL-Lite-CT, EQ-5D-5L, SF-36, and a study-specific Patient Global Impression of Status (PGIS) item.
Participants will attend six study visits over 52 weeks (Weeks 0, 8, 16, 24, 36, and 52), including anthropometric measurements, vital signs, laboratory safety assessments, and adverse event monitoring. Optional biobanking of blood and urine samples will be offered at Visits 1, 4, and 6 for future research, subject to separate informed consent.
The primary analysis will follow the intention-to-treat principle, using an analysis of covariance (ANCOVA) model adjusted for baseline weight and stratification factors. Secondary continuous outcomes will be analyzed using mixed-model repeated measures (MMRM), and categorical outcomes using logistic regression. No interim analysis is planned.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Adults (male or female) aged ≥18 years.
- •History of bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) performed ≥12 months before enrollment.
- •Current BMI ≥30 kg/m².
- •Evidence of suboptimal weight loss, defined as percentage total weight loss (%TWL) since surgery of less than 25% (defined as the percentage of weight loss comparing current body weight with body weight before surgery).
- •Absence of recent weight loss (defined as <5% reduction in body weight over the 6 months prior to screening); participants may be weight stable (<5% variation in body weight over the 6 months prior to screening) or have experienced weight gain.
- •In the investigator's opinion, well-motivated, capable, and willing to comply with study procedures.
- •For male participants: male participants with partners of childbearing potential should be willing to use reliable contraceptive methods throughout the study and for 5 half-lives of study drug plus 90 days, corresponding to 4 months after the last injection.
- •For female participants:
- •a. Female participants not of childbearing potential may participate and include those who are: i. infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal ligation), congenital anomaly such as Mullerian agenesis ii. postmenopausal, defined as either:
- •a woman at least 40 years of age with an intact uterus, not on hormone therapy, who has cessation of menses for at least 1 year without an alternative medical cause, AND a follicle-stimulating hormone ≥40mIU/mL; women in this category must test negative in pregnancy test prior to study entry
- •a woman 55 or older not on hormone therapy, who has had at least 12 months of spontaneous amenorrhea
- •a woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy b. Female participants of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) must:
- •test negative for pregnancy at Visit 1 based on a serum pregnancy test
- •if sexually active, agree to use 2 forms of effective contraception, where at least 1 form is highly effective, for the duration of the trial and for 30 days thereafter
- •not be breastfeeding
- •Provision of written informed consent prior to any study-specific procedures.
排除标准
- •Use of a GLP-1 receptor agonist (GLP-1 RA) or any other GLP-1-based therapy at present or within the past 6 months.
- •Prescription of a GLP-1 RA or other GLP-1-based therapy within the past 12 months that could not be initiated or maintained due to drug supply shortages.
- •Have a planned surgical treatment, endoscopic and/or device-based therapy for obesity during the period of the study.
- •History of type 1 diabetes or uncontrolled type 2 diabetes (HbA1c >10%).
- •Type 2 diabetes currently treated with insulin or sulfonylureas.
- •Have a known clinically significant gastric emptying abnormality (for example, severe diabetic gastroparesis or gastric outlet obstruction) or chronically take drugs that directly affect GI motility.
- •Have had a history of chronic or acute pancreatitis.
- •Have NYHA Functional Classification III or IV heart failure.
- •Have thyroid-stimulating hormone (TSH) outside of the reference range at screening visit.
- •Have obesity induced by other endocrinologic disorders (for example, Cushing Syndrome) or diagnosed monogenetic or syndromic forms of obesity (for example, Melanocortin 4 Receptor deficiency or Prader Willi Syndrome).
- •Have a history of significant active or unstable Major Depressive Disorder or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 years.
- •Have any lifetime history of a suicide attempt.
- •Have a family or personal history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia (MEN) Syndrome type
- •Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
- •Participation in another clinical study with an investigational product during the last month.
- •Unwilling or unable to sign the informed consent form.
- •History of active malignancy within the past 5 years (except adequately treated non-melanoma skin cancer or in situ carcinoma of the cervix).
- •Known hypersensitivity or contraindication to tirzepatide or any of its excipients.
- •Have severe hepatic impairment (Child-Pugh class C).
- •Have severe renal impairment (eGFR <30 mL/min/1.73 m² using CKD-EPI formula).
- •Are receiving or have received within 3 months prior to screening chronic (>2 weeks or 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intra-articular, or inhaled preparations) or have evidence of a significant, active autoimmune abnormality (for example, lupus or rheumatoid arthritis) that has required (within the last 3 months) or is likely to require, in the opinion of the investigator, concurrent treatment with systemic glucocorticoids (excluding topical, intraocular, intranasal, intra-articular or inhaled preparations) in the next 12 months.
- •For female patients, pregnancy, breastfeeding, or planning pregnancy during the study period.
- •Any condition which, in the investigator's opinion, may jeopardize the subject's safety or compliance with the protocol (e.g., severe psychiatric illness, alcohol or substance abuse).
研究组 & 干预措施
Placebo
Participants will receive matching placebo (identical prefilled syringe) once weekly by subcutaneous injection, self-administered at home, following the same up-titration schedule and visit schedule as the tirzepatide arm, for a total of 52 weeks.
干预措施: Placebo (Drug)
Tirzepatide
Participants will receive tirzepatide once weekly by subcutaneous injection, self-administered at home. Treatment will start at 2.5 mg once weekly, with up-titration in 2.5 mg increments every 4 weeks (5 mg, 7.5 mg, 10 mg, 12.5 mg, up to 15 mg), according to tolerability, up to the maximum tolerated dose or 15 mg once weekly. Treatment will continue for a total of 52 weeks.
干预措施: Tirzepatide (Drug)
结局指标
主要结局
Percentage Change in Body Weight from Baseline to Week 52
时间窗: Baseline (Week 0) to Week 52
To assess the effect of tirzepatide versus placebo on the percentage change in body weight relative to baseline at week 52
次要结局
- Change in Body Weight(From baseline to Weeks 8, 16, 24, 36, and 52)
- Change in Body Mass Index (BMI)(From baseline to Weeks 8, 16, 24, 36, and 52)
- Change in Waist Circumference(From baseline to Weeks 8, 16, 24, 36, and 52)
- Change in Blood Pressure(From baseline to Weeks 8, 16, 24, 36, and 52)
- Change in Glycated Hemoglobin (HbA1c)(From baseline to Week 52)
- Change in Fasting Glucose(From baseline to Week 52)
- Change in Lipid Profile(From baseline to Week 52)
- Change in Kidney Function(From baseline to Week 52)
- Change in Liver Profile(From baseline to Week 52)
- Change in High-Sensitivity C-Reactive Protein (hs-CRP)(From baseline to Week 52)
- Proportion of Participants Achieving Clinically Meaningful Weight Loss(At Week 52)
- Change in Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) Score(From baseline to Week 52)
- Change in EQ-5D-5L Score(From baseline to Week 52)
- Change in Short Form 36 version 2 (SF-36v2) Score(From baseline to Week 52)
- Change in Patient Global Impression of Status (PGIS)(From baseline to Week 52)