Phase 1/2 Prospective Double-blind, Placebo-controlled Randomized Clinical Trial Using Losartan to Treat Grade II and III Hamstring Strains

The goal of this study is to determine safety and tolerability of Losartan when used for treatment of an acute grade II or III hamstring strain and determining the effect of losartan on recovery of hamstring muscle function. Subjects will be adults age 18 and older with grade 2 or 3 hamstring injury who participate in greater than 100 hours per year in Level 1 or Level 2 athletics or have a similar activities or physical work load (e.g. military personnel). Subjects will undergo examination, MRI, and functional assessment before, during, and after 4 weeks of losartan (50mg QD) or placebo.

Study Overview

• Status: Terminated
• Conditions: Hamstring Injury
• Intervention / Treatment: Drug: placebo; Drug: Losartan

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: James Irrgang, PT,PhD; Email: jirrgang@pitt.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. 18 years of age and older;
2. Have had grade II or III hamstring injury within the 7 days prior to enrollment;
3. Greater than 100 hours per year in Level I (football, basketball, or soccer) or Level II (racquet sports, skiing, manual labor occupations/heavy physical work) and activities that require running and sprinting;
4. Agree to take study medications as prescribed

Exclusion Criteria:

1. Have had previous hamstring injury on the same side or chronic symptoms;
2. Have an injury that requires surgical intervention (e.g. avulsion with associated bony involvement, grade III complete tears);
3. Have concurrent lower back symptoms;
4. Pregnant or breast feeding;
5. Is a smoker;
6. Has contraindications for Losartan therapy (hypersensitivity to Losartan, hepatic involvement);
7. Currently use angiotensin I converting enzyme inhibitor (ACEI)/ Angiotensin II receptor blocker (ARB);
8. Have hypertension (blood pressure greater than or equal to 140 mmHg systolic pressure or greater than or equal to 90 mmHg diastolic pressure);
9. Have hypotension (blood pressure less than or equal to 90 mmHg systolic pressure or less than or equal to 60 mmHg diastolic pressure);
10. Have orthostatic hypotension defined as a drop in systolic pressure greater than or equal to 2 0mmHg or a drop in diastolic blood pressure greater than or equal to 10 mmHg or reports of lightheadedness or dizziness upon standing;
11. Have diabetes mellitus, cardiovascular, renal or hepatic co-morbidities;
12. Sickle cell anemia/trait;

13. Have contraindications for MRI - including:

    • Prior surgery for an aneurysm;
    • Have cardiac pacemaker;
    • Have metal fragments in the eyes, brain, or spinal cord from shrapnel, metal work, or welding;
    • Have surgical implants, such as ear implant or neurostimulator;
    • Have a history of claustrophobia;
    • Have a history of not tolerating previous MRI scans without medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: losartan; Subjects will taken 50mg of losartan per day for 4 weeks	Drug: Losartan
Placebo Comparator: placebo; Subjects will be given placebo to replicate appearance of losartan pills. Placebo pill will be taken once per day.	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reported effects of losartan for hamstring injury for safety and tolerability	Directly related to specific aim 1- Side effects, safety, and tolerability will be monitored by measuring vital signs, lab values via blood work, and number of adverse events, serious adverse events, and patient reported side effects.	4 weeks
Return to prior level of function	Return to prior level of function will be measured by the number of days from injury to full, unrestricted return to practice.	12 months
Recurrence of injury	Number of recurrent injuries will be monitored during the duration of the subjects participation.	12 months
Recovery of hamstring muscle function and structure	Related to specific aim 2, hamstring muscle function of the injured leg will be measured and compared to the contralateral leg using isometric hamstring force at 6 weeks and 6 months. Hamstring function is measured by comparing pre-treatment MRI to MRI at 6 months post-treatment	6 weeks; 6 months

Collaborators and Investigators

• Sponsor: James J. Irrgang
• Collaborators: Brooke Army Medical Center; Wake Forest University

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2016
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: September 26, 2014
• First Submitted That Met QC Criteria: October 8, 2014
• First Posted (Estimated): October 13, 2014

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: STUDY19100320; W81XWH-14-2-0003 (Other Grant/Funding Number: US Army Medical Research Acquisition Activity)