The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin

The Effect of Exercise on Pharmacodynamics and Pharmacokinetics of a Single Dose of Unfractionated Heparin: A Randomized, Controlled, Cross-over Study

The aim of this project is to assess the influence of exercise on pharmacokinetics (PK) and pharmacodynamics (PD) of a single dose of subcutaneously (sc) administered unfractionated heparin (UFH). It is hypothesized that exercise will increase the systemic exposure (PK) and therefore the clinical effects (PD) of the sc administered UFH.

To assess this, healthy male volunteers will be included in a controlled, randomized, crossover study, where they, on four separate days, will have UFH injected sc in the thigh, followed by different exercise interventions (one per experimental day). Blood sampling, with the aim of assessing PK and PD will be performed during the following hours.

Study Overview

• Status: Completed
• Conditions: Blood Coagulation Disorder
• Intervention / Treatment: Drug: Unfractionated heparin; Behavioral: No exercise; Behavioral: Double-legged cycle ergometer exercise; Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the exercising leg; Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the non-exercising leg

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Bispebjerg-Frederiksberg Hospital, Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body weight 50 kg or more
• Body Mass Index 18.5-25 kg/m2
• Acceptance of not drinking alcohol for 24 hours before to 24 hours after dosing of study drug
• Acceptance of not performing physical activity for 24 hours before to 24 hours after dosing of study drug
• Signed informed consent form

Exclusion Criteria:

• History or sign of bleeding disorders
• History or sign of kidney disease
• History or sign of liver disease
• Average systolic blood pressure <100 mmHg or >140 mmHg and/or average diastolic blood pressure <60 mmHg or >90 mmHg (average of three measurements performed at screening).
• Daily pharmaceutical treatment
• Contraindication to increased levels of physical activity (10)
• Smoking or other regular use of any form of nicotine products during the study period and the previous 3 months.
• Current or prior participation (within 3 months before screening) in other clinical trials that might affect the results of this study (judged by the investigator).
• Previous treatment with heparins
• Low levels of anti-thrombin (P-antitrombin(enz.) <0,80 kIU/L)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Unfractionated heparin + No exercise; 15,000 units of unfractionated heparin will be administered in the thigh. No exercise will be performed afterwards.	Drug: Unfractionated heparin; 15,000 units of unfractionated heparin administered in the thigh; Behavioral: No exercise; No exercise
Experimental: Unfractionated heparin + Double-legged cycle ergometer exercise; 15,000 units of unfractionated heparin will be administered in the thigh. Double-legged cycle ergometer exercise will be performed for 1 hour afterwards	Drug: Unfractionated heparin; 15,000 units of unfractionated heparin administered in the thigh; Behavioral: Double-legged cycle ergometer exercise; One hour of double-leg cycle ergometer exercise
Experimental: Unfractionated heparin + Single-legged ipsilateral cycle ergometer exercise; 15,000 units of unfractionated heparin will be administered in the thigh. Single-legged cycle ergometer exercise in leg where unfractionated heparin injection is given will be performed for 1 hour afterwards	Drug: Unfractionated heparin; 15,000 units of unfractionated heparin administered in the thigh; Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the exercising leg; One hour of single-leg cycle ergometer exercise, after unfractionated heparin injection in the ipsilateral leg
Experimental: Unfractionated heparin + Single-legged contralateral cycle ergometer exercise; 15,000 units of unfractionated heparin will be administered in the thigh. Single-legged cycle ergometer exercise in contralateral leg to where unfractionated heparin injection is given will be performed for 1 hour afterwards	Drug: Unfractionated heparin; 15,000 units of unfractionated heparin administered in the thigh; Behavioral: Single-legged cycle ergometer exercise, with unfractionated heparin injection in the non-exercising leg; One hour of single-leg cycle ergometer exercise, after unfractionated heparin injection in the ipsilateral leg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Difference between interventions in change in incremental activated partial thromboplastin time (aPTT)	Peak aPTT for 1-8 hours after unfractionated heparin (UFH) injection

Secondary Outcome Measures

Outcome Measure	Time Frame
Difference between interventions in change in incremental plasma heparin	Peak plasma heparin for 1-8 hours after UFH injection
Difference between interventions in mean incremental aPTT	1-8 hours after UFH injection
Difference between interventions in mean incremental plasma heparin	1-8 hours after UFH injection
Difference between interventions in change in aPTT	4 hours after UFH injection
Difference between interventions in change in plasma heparin	4 hours after UFH injection
Difference between interventions in mean incremental natriuretic peptides	1-8 hours after UFH injection
Difference between interventions in mean incremental follistatin	1-8 hours after UFH injection

Collaborators and Investigators

• Sponsor: Kristian Karstoft
• Investigators: Principal Investigator: Kristian Karstoft, MD, DMSc, Bispebjerg-Frederiksberg Hospital, Department of Clinical Pharmacology

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2023
• Primary Completion (Actual): February 13, 2024
• Study Completion (Actual): May 1, 2024

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: December 8, 2023
• First Posted (Actual): December 18, 2023

Study Record Updates

• Last Update Posted (Actual): June 26, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Blood Coagulation Disorders; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: 2023-000150-20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No