NCT07483801

Brief Summary

What is the research question? Semaglutide and tirzepatide cause weight loss and blood pressure reduction. However, weight loss only partially explains the blood pressure reduction. Based on previous studies, there might be direct effects in the cardiovascular system. In forearm blood flow studies, semaglutide and tirzepatide will be infused into the brachial artery to investigate their effects on the function of blood vessels. In systemic studies, semaglutide and tirzepatide will be infused into systemic circulation to investigate their effects on heart and blood vessels. There are three different populations being looked at for this study: participants with normal weight and normal blood pressure, participants with obesity and normal blood pressure, and participants with obesity and high blood pressure. There are six sub-studies each with different visit schedules. The minimum participant study duration (including follow-up phone call) would be 2 days, while the maximum participant study duration would be approximately 2 - 2.5 months. The overall study duration is expected to be approximately 18 months.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
112

participants targeted

Target at P50-P75 for phase_4 cardiovascular-diseases

Timeline
22mo left

Started Mar 2026

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress11%
Mar 2026Apr 2028

First Submitted

Initial submission to the registry

February 3, 2026

Completed
26 days until next milestone

Study Start

First participant enrolled

March 1, 2026

Completed
18 days until next milestone

First Posted

Study publicly available on registry

March 19, 2026

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2028

Last Updated

March 19, 2026

Status Verified

March 1, 2026

Enrollment Period

1.1 years

First QC Date

February 3, 2026

Last Update Submit

March 17, 2026

Conditions

Cardiovascular Diseases

Keywords

MetabolicEndocrineSemaglutidetirzepatideweight losshypertension)

Outcome Measures

Primary Outcomes (21)

  • Sub-study 1A:Change in forearm blood flow parameters after infusion of semaglutide (Ratio)

    Ratio, expressed as a number (no units as this is a ratio)

    2-2.5 months from screening to follow-up

  • Sub-study 1A:Change in forearm blood flow parameters after infusion of semaglutide (Absolute flow)

    Absolute flow in the infused arm, in mL/min/100 mL

    2-2.5 months from screening to follow-up

  • Sub-study 1A: Change in forearm blood flow parameters after infusion of semaglutide (Percentage Change)

    Percentage change in the infused arm, in %

    2-2.5 months from screening to follow-up

  • Sub-study 1B: Change in forearm blood flow parameters after infusion of tirzepatide (Absolute flow)

    Absolute flow in the infused arm, in mL/min/100 mL

    2-2.5 months from screening to follow-up

  • Sub-study 1B: Change in forearm blood flow parameters after infusion of tirzepatide (Ratio)

    Ratio, expressed as a number (no units as this is a ratio)

    2-2.5 months from screening to follow-up

  • Sub-study 1B: Change in forearm blood flow parameters after infusion of tirzepatide (Percent Change)

    Percentage change in the infused arm, in %

    2-2.5 months from screening to follow-up

  • Sub-study 1C: Change in forearm blood flow parameters after infusion of semaglutide or tirzepatide or saline (Absolute flow)

    Absolute flow in the infused arm, in mL/min/100 mL

    2-2.5 months from screening to follow-up

  • Sub-study 1C: Change in forearm blood flow parameters after infusion of semaglutide or tirzepatide or saline (Ratio)

    Ratio, expressed as a number (no units as this is a ratio)

    2-2.5 months from screening to follow-up

  • Sub-study 1C: Change in forearm blood flow parameters after infusion of semaglutide or tirzepatide or saline (Percentage change)

    Percentage change in the infused arm, in %

    2-2.5 months from screening to follow-up

  • Sub-study 2A: Changes in cardiovascular haemodynamic variables after administration of semaglutide (Blood pressure)

    Blood pressure measured in mmHg

    2-2.5 months from screening to follow-up

  • Sub-study 2A: Changes in cardiovascular haemodynamic variables after administration of semaglutide (Heart rate)

    Heart rate measured in beats per minute (bpm)

    2-2.5 months from screening to follow-up

  • Sub-study 2A: Changes in cardiovascular haemodynamic variables after administration of semaglutide (Cardiac output)

    Cardiac output measured in L/min

    2-2.5 months from screening to follow-up

  • Sub-study 2A: Changes in cardiovascular haemodynamic variables after administration of semaglutide (Vascular resistance)

    Vascular resistance measured in dynes⋅sec⋅cm5

    2-2.5 months from screening to follow-up

  • Sub-study 2B: Changes in cardiovascular haemodynamic variables after administration of tirzepatide (Blood pressure)

    Blood pressure measured in mmHg

    2-2.5 months from screening to follow-up

  • Sub-study 2B: Changes in cardiovascular haemodynamic variables ) after administration of tirzepatide (Heart rate)

    Heart rate measured in beats per minute (bpm)

    2-2.5 months from screening to follow-up

  • Sub-study 2B: Changes in cardiovascular haemodynamic variables after administration of tirzepatide (Cardiac output)

    Cardiac output measured in L/min

    2-2.5 months from screening to follow-up

  • Sub-study 2B: Changes in cardiovascular haemodynamic variables after administration of tirzepatide (Vascular resistance)

    Vascular resistance measured in dynes⋅sec⋅cm5

    2-2.5 months from screening to follow-up

  • Sub-study 2C: Changes in cardiovascular haemodynamic variables after administration of semaglutide or tirzepatide or saline (Blood pressure)

    Blood pressure measured in mmHg

    2-2.5 months from screening to follow-up

  • Sub-study 2C: Changes in cardiovascular haemodynamic variables after administration of semaglutide or tirzepatide or saline (Heart rate)

    Heart rate measured in beats per minute (bpm)

    2-2.5 months from screening to follow-up

  • Sub-study 2C: Changes in cardiovascular haemodynamic variables after administration of semaglutide or tirzepatide or saline (Cardiac output)

    Cardiac output measured in L/min

    2-2.5 months from screening to follow-up

  • Sub-study 2C: Changes in cardiovascular haemodynamic variables after administration of semaglutide or tirzepatide or saline (Vascular resistance)

    Vascular resistance measured in dynes⋅sec⋅cm5

    2-2.5 months from screening to follow-up

Study Arms (6)

Sub-study 1A

EXPERIMENTAL

Intra-arterial infusion of semaglutide

Drug: semaglutide

Sub-study 1B

EXPERIMENTAL

Intra-arterial infusion of Tirzepatide

Drug: Tirzepatide

Sub-study 1C

EXPERIMENTAL

Intra-arterial infusion of Saline, Semaglutide and Tirzepatide

Drug: semaglutideDrug: Tirzepatide

Sub-study 2A

EXPERIMENTAL

Slow intravenous bolus of Semaglutide

Drug: semaglutide

Sub-study 2B

EXPERIMENTAL

Slow intravenous bolus of Tirzepatide

Drug: Tirzepatide

Sub-study 2C

EXPERIMENTAL

Slow intravenous bolus of Semaglutide and Tirzepatide

Drug: semaglutideDrug: Tirzepatide

Interventions

semaglutideDRUG

Semaglutide: GLP-1 analogue

Sub-study 1ASub-study 1CSub-study 2ASub-study 2C
TirzepatideDRUG

Tirzepatide: dual GIP/GLP-1 receptor agonist

Sub-study 1BSub-study 1CSub-study 2BSub-study 2C

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Have given written informed consent to participate
  • Aged 18 to 50 years (inclusive)
  • Females must be post/peri-menopausal or if of child-bearing potential they are required to use adequate contraception and to have a negative pregnancy test (performed at each visit)
  • Current non-smoker
  • Body mass index (BMI) in range 18.5-24.9 kg/m2
  • Clinic brachial systolic blood pressure \<140 mmHg and diastolic blood pressure \<90 mmHg
  • Have given written informed consent to participate
  • Aged 18 to 50 years (inclusive)
  • Male or female
  • Females must be post/peri-menopausal or if of child-bearing potential they are required to use adequate contraception and to have negative pregnancy test (performed at each visit)
  • Current non-smoker
  • BMI ≥30 kg/m2
  • Clinic brachial systolic blood pressure \<140 mmHg and diastolic blood pressure \<90 mmHg
  • Have given written informed consent to participate
  • Aged 18 to 50 years (inclusive)
  • +5 more criteria

You may not qualify if:

  • Regular use of medications with vasoactive or cardiac effects in normotensive individuals; inability or unwillingness to omit anti-hypertensive medications on the morning of the study visits in hypertensive individuals
  • Hypersensitivity to any of the study drugs or excipients
  • Known clinically significant valvular heart disease
  • Implanted pacemaker or implantable cardioverter defibrillator (ICD)
  • Known active malignancy
  • Known renal impairment (creatinine \>150µmol/L)
  • Clinically significant neurological disease
  • History of scleroderma
  • Current pregnancy, breastfeeding
  • Current involvement in the active treatment phase of other research studies (excluding observational/non-interventional)
  • Second or third-degree AV block, sino-atrial block, sick sinus syndrome
  • Known HIV, hepatitis B or C
  • Needle phobia
  • Participants treated with formal anticoagulant therapy such as, but not limited to, heparin or warfarin
  • Diagnosis of Type 1 or Type 2 Diabetes Mellitus or current usage of insulin or other injectable drugs for the treatment of diabetes such as but not limited to GLP-1 and GIP receptor agonists
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB20QQ, United Kingdom

Location

MeSH Terms

Conditions

Cardiovascular DiseasesWeight LossHypertension

Interventions

semaglutideTirzepatide

Condition Hierarchy (Ancestors)

Body Weight ChangesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsVascular Diseases

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide ReceptorsReceptors, G-Protein-CoupledReceptors, Cell SurfaceMembrane ProteinsProteinsAmino Acids, Peptides, and ProteinsReceptors, Gastrointestinal HormoneReceptors, Peptide

Central Study Contacts

Guneswary Thaygaraja, Msc Genomic Medicine

CONTACT

01223 349762cuh.cambs.cardiovascular@nhs.net

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Consultant Clinical Pharmacologist & Physician

Study Record Dates

First Submitted

February 3, 2026

First Posted

March 19, 2026

Study Start

March 1, 2026

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

April 1, 2028

Last Updated

March 19, 2026

Record last verified: 2026-03

Locations

GB(1)