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Tirzepatide Titration to Reduce Side Effects in Individuals With Obesity (TiTRE)

7 de julio de 2026 actualizado por: Dasman Diabetes Institute

Tirzepatide Titration to Reduce Side Effects (TiTRE) in Individuals With Obesity

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:

  1. Does flexible, symptom-guided titration reduce nausea and vomiting compared with standard per-label titration?
  2. 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.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

68

Fase

  • No aplica

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Kuwait
      • Kuwait City, Kuwait, 15462
        • Reclutamiento
        • Dasman Diabetes Institute
        • Investigador principal:
          • Ebaa AlOzairi
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

Inclusion Criteria:

  1. Adults aged 18 years and older
  2. A diagnosis of obesity (BMI ≥ 27 kg/m2) at screening with self-reported unsuccessful dietary efforts to lose weight.
  3. No diagnosis of diabetes mellites.
  4. Able to understand and sign the consent form
  5. Able to undergo DEXA scan.

Exclusion Criteria:

  • 1. History of type 1 or type 2 diabetes mellites. 2. 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. 4. 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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Per-label arm (Control)
Participants receive tirzepatide with dose escalation according to the manufacturer's prescribing information.
Droga: Tirzepatide (Per-label titration)
Tirzepatide is administered by subcutaneous injection once weekly. Dose escalation follows the manufacturer's prescribing information, with advancement through labeled dose levels at prespecified intervals to the assigned maintenance dose
Experimental: Flexible titration arm (Intervention)
Participants receive tirzepatide administered with a flexible dose escalation schedule.
Droga: Tirzepatide (Flexible titration)
Tirzepatide is administered by subcutaneous injection once weekly. Dose escalation follows a flexible titration schedule as defined in the study protocol.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Vomiting episodes per patient assessed using the Modified Index of Nausea, Vomiting, and Retching (M-INVR)
Periodo de tiempo: From enrollment (at baseline) to the end of treatment at 76 weeks.

Vomiting episodes per patient will be assessed using the validated Modified Index of Nausea, Vomiting, and Retching (M-INVR). The vomiting component is administered weekly, with scores ranging from 0 (no vomiting) to 4 (severe or frequent vomiting), where higher scores indicate worse outcomes.

Vomiting burden will be summarized as:

  • Weekly vomiting severity scores based on M-INVR, and
  • An exposure-adjusted rate of vomiting episodes (episodes per patient-week), calculated by dividing the total number of reported vomiting episodes by the total duration of follow-up for each participant.

This approach accounts for differences in treatment duration and follow-up time.
From enrollment (at baseline) to the end of treatment at 76 weeks.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Incidence, frequency, and duration of vomiting assessed using the MASCC Antiemesis Tool - Modified Index of Nausea and Vomiting (M-INVR)
Periodo de tiempo: Baseline to Week 76

Vomiting is assessed weekly using the MASCC Antiemesis Tool - Modified Index of Nausea and Vomiting (M-INVR), a validated patient-reported outcome measure.

The vomiting subscale score is calculated as the sum of relevant vomiting items, with scores ranging from 0 to 16, where higher scores indicate greater incidence, frequency, and duration of vomiting (worse outcome).
Baseline to Week 76
Change in body weight
Periodo de tiempo: Baseline to Week 76
Absolute and percentage change in body weight from baseline.
Baseline to Week 76
Proportion of participants remaining on active study medication
Periodo de tiempo: Week 76
Number of participants continuing to receive active study medication at the end of the trial.
Week 76
Change in glycated hemoglobin (HbA1c)
Periodo de tiempo: Baseline to Week 76
Change in HbA1c from baseline.
Baseline to Week 76
Change in lean body mass assessed by dual-energy X-ray absorptiometry (DEXA)
Periodo de tiempo: Baseline to Week 76
Change in total lean body mass measured by dual-energy X-ray absorptiometry (DEXA).
Baseline to Week 76
Change in visceral adiposity assessed by dual-energy X-ray absorptiometry (DEXA)
Periodo de tiempo: Baseline to Week 76
Change in visceral adipose tissue measured by dual-energy X-ray absorptiometry (DEXA).
Baseline to Week 76
Change in fat body mass assessed by dual-energy X-ray absorptiometry (DEXA)
Periodo de tiempo: Baseline to Week 76
Change in total fat body mass measured by dual-energy X-ray absorptiometry (DEXA).
Baseline to Week 76
Change in Alanine Aminotransferase (ALT)
Periodo de tiempo: Baseline to Week 76
Change from baseline in serum alanine aminotransferase (ALT) levels in U/L, measured using standard laboratory methods.
Baseline to Week 76
Change in Aspartate Aminotransferase (AST)
Periodo de tiempo: Baseline to Week 76
Change from baseline in serum aspartate aminotransferase (AST) levels in U/L, measured using standard laboratory methods.
Baseline to Week 76
Change in Gamma-Glutamyl Transferase (GGT)
Periodo de tiempo: Baseline to Week 76
Change from baseline in serum gamma-glutamyl transferase (GGT) levels in U/L, measured using standard laboratory methods.
Baseline to Week 76
Change in Alkaline Phosphatase (ALP)
Periodo de tiempo: Baseline to Week 76
Change from baseline in serum alkaline phosphatase (ALP) levels in U/L, measured using standard laboratory methods.
Baseline to Week 76
Change in Fibrosis-4 (FIB-4) index
Periodo de tiempo: Baseline to Week 76

Change from baseline in the Fibrosis-4 (FIB-4) index, a composite score calculated as:

FIB-4 = (Age × AST) / (Platelet count × √ALT), where age is measured in years, AST and ALT in U/L, and platelet count in 10⁹/L. The FIB-4 index is reported as a unitless value, with higher values indicating greater liver fibrosis. Values typically range from approximately 0 to 10.
Baseline to Week 76
Change in Total Cholesterol
Periodo de tiempo: Baseline to Week 76
Change from baseline in fasting total cholesterol levels measured using standard laboratory methods.
Baseline to Week 76
Change in Low-Density Lipoprotein Cholesterol (LDL-C)
Periodo de tiempo: Baseline to Week 76
Change from baseline in fasting low-density lipoprotein cholesterol (LDL-C) levels measured using standard laboratory methods.
Baseline to Week 76
Change in High-Density Lipoprotein Cholesterol (HDL-C)
Periodo de tiempo: Baseline to Week 76
Change from baseline in fasting high-density lipoprotein cholesterol (HDL-C) levels measured using standard laboratory methods.
Baseline to Week 76
Change in Triglycerides
Periodo de tiempo: Baseline to Week 76
Change from baseline in fasting triglyceride levels measured using standard laboratory methods.
Baseline to Week 76
Change in estimated glomerular filtration rate (eGFR)
Periodo de tiempo: Baseline to Week 76
Change from baseline in estimated glomerular filtration rate (eGFR) calculated using a standard equation.
Baseline to Week 76
Change in serum creatinine
Periodo de tiempo: Baseline to Week 76
Change from baseline in serum creatinine measured using standard laboratory methods.
Baseline to Week 76
Change in urinary microalbumin
Periodo de tiempo: Baseline to Week 76
Change from baseline in urinary microalbumin concentration measured using standard laboratory methods.
Baseline to Week 76
Change in urine albumin-to-creatinine ratio (ACR)
Periodo de tiempo: Baseline to Week 76
Change from baseline in urine albumin-to-creatinine ratio (ACR) measured using standard laboratory methods.
Baseline to Week 76
Change in thyroid-stimulating hormone (TSH)
Periodo de tiempo: Baseline to Week 76
Change from baseline in serum thyroid-stimulating hormone (TSH) measured using standard laboratory methods.
Baseline to Week 76
Change in free thyroxine (free T4)
Periodo de tiempo: Baseline to Week 76
Change from baseline in serum free thyroxine (free T4) measured using standard laboratory methods.
Baseline to Week 76
Change in interleukin-6 (IL-6)
Periodo de tiempo: Baseline to Week 76
Change from baseline in circulating interleukin-6 (IL-6) concentration measured using standard laboratory methods.
Baseline to Week 76
Change in interleukin-10 (IL-10)
Periodo de tiempo: Baseline to Week 76
Change from baseline in circulating interleukin-10 (IL-10) concentration measured using standard laboratory methods.
Baseline to Week 76
Change in interleukin-1 receptor antagonist (IL-1Ra)
Periodo de tiempo: Baseline to Week 76
Change from baseline in circulating interleukin-1 receptor antagonist (IL-1Ra) concentration measured using standard laboratory methods.
Baseline to Week 76
Change in tumor necrosis factor-alpha (TNF-α)
Periodo de tiempo: Baseline to Week 76
Change from baseline in circulating tumor necrosis factor-alpha (TNF-α) concentration measured using standard laboratory methods.
Baseline to Week 76
Change in health-related quality of life assessed using the 36-Item Short Form Health Survey (SF-36)
Periodo de tiempo: Baseline to Week 76

Health-related quality of life is assessed using the 36-Item Short Form Health Survey (SF-36), a validated patient-reported outcome measure.

The SF-36 yields an overall score ranging from 0 to 100, with higher scores indicating better health-related quality of life.
Baseline to Week 76
Change in dietary intake patterns
Periodo de tiempo: Baseline to Week 76
Changes in macronutrient composition and total caloric intake assessed using multiple-pass 24-hour dietary recalls.
Baseline to Week 76
Incidence of adverse events and laboratory abnormalities
Periodo de tiempo: Baseline to Week 76
Incidence of treatment-emergent adverse events and clinically significant laboratory abnormalities.
Baseline to Week 76
Change in retinal nerve fiber layer thickness assessed by optical coherence tomography (OCT)
Periodo de tiempo: Baseline to Week 76
Change from baseline in retinal nerve fiber layer thickness measured by optical coherence tomography
Baseline to Week 76
Change in arterial stiffness measured by pulse wave velocity (PWV)
Periodo de tiempo: Baseline to Week 76
Change from baseline in arterial stiffness assessed by carotid-femoral pulse wave velocity.
Baseline to Week 76
Change in sudomotor function assessed by Sudoscan
Periodo de tiempo: Baseline to Week 76
Change from baseline in sudomotor function measured by electrochemical skin conductance using Sudoscan.
Baseline to Week 76
Treatment Persistence and Discontinuation
Periodo de tiempo: Up to 76 weeks
Treatment persistence will be assessed by the proportion of participants remaining on active study medication at week 76. Treatment discontinuation and reasons for discontinuation will be recorded throughout the study and categorized as gastrointestinal adverse events (including nausea and vomiting), other adverse events, lack of efficacy, participant preference, protocol non-adherence, loss to follow-up, pregnancy, investigator decision, or other specified reasons.
Up to 76 weeks

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Dasman Diabetes Institute

Colaboradores

University of Ulster

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

15 de mayo de 2026

Finalización primaria (Estimado)

15 de mayo de 2029

Finalización del estudio (Estimado)

31 de diciembre de 2029

Fechas de registro del estudio

Enviado por primera vez

19 de abril de 2026

Primero enviado que cumplió con los criterios de control de calidad

5 de mayo de 2026

Publicado por primera vez (Actual)

8 de mayo de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

8 de julio de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

7 de julio de 2026

Última verificación

1 de julio de 2026

Más información

Términos relacionados con este estudio

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • RA HM-2026-06

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

producto fabricado y exportado desde los EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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