Tirzepatide Titration to Reduce Side Effects (TiTRE) in Individuals With Obesity
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 68
- 试验地点
- 1
研究概览
简要总结
The goal of this clinical trial is to determine whether a flexible, symptom-guided titration strategy for tirzepatide can reduce gastrointestinal side effects while maintaining weight-loss effectiveness in adults with obesity without diabetes. The main questions it aims to answer are:
- Does flexible, symptom-guided titration reduce nausea and vomiting compared with standard per-label titration?
- Does flexible titration achieve weight loss comparable to standard titration?
Researchers will compare standard per-label titration with a click-based, symptom-guided titration approach to assess differences in tolerability and treatment effectiveness.
Participants will:
- Be randomly assigned to standard or flexible tirzepatide titration
- Use a click-based dosing method that allows small dose increases based on tolerability (flexible group)
- Attend study visits over 76 weeks for safety and outcome assessments
This study addresses the lack of evidence for individualized titration strategies in obesity treatment and aims to improve tolerability, adherence, and long-term treatment outcomes.
详细描述
Tirzepatide is an effective treatment for obesity, but gastrointestinal adverse events during dose escalation may limit tolerability and adherence. Current labeling recommends a fixed titration schedule that does not account for individual differences in symptom tolerance. Evidence supporting individualized titration strategies in obesity treatment remains limited.
This randomized clinical trial aims to evaluate whether a flexible, symptom-guided titration strategy for tirzepatide can reduce gastrointestinal side effects while maintaining weight-loss effectiveness in adults with obesity without diabetes. Participants will be randomly assigned to either standard per-label titration or a flexible, click-based titration approach that allows smaller dose increments based on individual tolerability.
Participants in the standard group will follow the approved fixed dose-escalation schedule, while participants in the flexible group will advance doses according to gastrointestinal symptom severity, with the goal of minimizing nausea and vomiting. All participants will attend study visits over 76 weeks for assessment of weight change, tolerability, safety, and treatment adherence.
This study will compare gastrointestinal tolerability and weight-loss outcomes between titration strategies and aims to inform individualized dosing approaches that may improve adherence and long-term obesity treatment outcomes.
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
- None
盲法说明
Blinding will be maintained for outcome assessors and data analysts to minimize bias. While participants cannot be blinded to treatment allocation due to the nature of the intervention, all personnel involved in outcome measurement and statistical analysis will remain unaware of group assignments. Procedures for maintaining blinding will include secure allocation concealment and restricted access to randomization codes.
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18 years and older
- •A diagnosis of obesity (BMI ≥ 27 kg/m2) at screening with self-reported unsuccessful dietary efforts to lose weight.
- •No diagnosis of diabetes mellites.
- •Able to understand and sign the consent form
- •Able to undergo DEXA scan.
排除标准
- •1. History of type 1 or type 2 diabetes mellites.
- •Obesity-related:
- •A self-reported change in body weight >5 kg (11 lbs) within 90 days before screening irrespective of medical records.
- •Treatment with any medication for the indication of obesity within the past 90 days before screening.
- •Previous or planned (during the trial period) obesity treatment with surgery or a weight-loss device. However, the following are allowed: (1) liposuction and/or abdominoplasty, if performed >1 year before screening; (2) lap banding, if the band has been removed >1 year before screening; (3) intragastric balloon, if the balloon has been removed >1 year before screening; or (4) duodenal-jejunal bypass sleeve, if the sleeve has been removed >1 year before screening.
- •Uncontrolled thyroid disease, defined as thyroid stimulating hormone >6.0 mIU/L or <0.4 mIU/L as measured by the central laboratory at screening.
- •3. Mental health:
- •History of major depressive disorder within 2 years before screening.
- •Diagnosis of other severe psychiatric disorder (e.g. schizophrenia, bipolar disorder).
- •A Patient Health Questionnaire-9 score of ≥15 at screening.
- •A lifetime history of a suicidal attempt.
- •Suicidal behavior within 30 days before screening.
- •General safety:
- •Use of non-herbal Chinese medicine or other non-herbal local medicine with unknown/unspecified content within 90 days before screening.
- •Presence of acute pancreatitis within the past 180 days prior to the day of screening.
- •History or presence of chronic pancreatitis.
- •Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.
- •Renal impairment measured as estimated glomerular filtration rate value of <15 mL/min/1.73 m2 as defined by KDIGO 2012 by the central laboratory at screening.
- •History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
- •Any of the following: myocardial infarction, stroke, hospitalization for unstable angina, or transient ischemic attack within the past 60 days prior to screening.
- •Subject presently classified as being in New York Heart Association Class IV.
- •Surgery scheduled for the duration of the trial, except for minor surgical procedures, in the opinion of the investigator.
- •Known or suspected abuse of alcohol or recreational drugs.
- •Known or suspected hypersensitivity to trial product(s) or related products.
- •Previous participation in this trial. Participation is defined as signed informed consent.
- •Participation in another clinical trial within 90 days before screening.
- •Female who is pregnant, breast-feeding, or intends to become pregnant, or is of child-bearing potential and not using a highly effective contraceptive method.
- •Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardize the subject's safety or compliance with the protocol.
研究组 & 干预措施
Flexible titration arm (Intervention)
Participants receive tirzepatide administered with a flexible dose escalation schedule.
干预措施: Tirzepatide (Flexible titration) (Drug)
Per-label arm (Control)
Participants receive tirzepatide with dose escalation according to the manufacturer's prescribing information.
干预措施: Tirzepatide (Per-label titration) (Drug)
结局指标
主要结局
未指定
次要结局
- Treatment Persistence and Discontinuation(Up to 76 weeks)