Phase 1/2 Prospective Double-Blind Placebo-Controlled Randomized Clinical Trial of Losartan to Treat Grade II & III Hamstring Strains

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 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; Cozaar
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
Recovery of Hamstring Muscle Function	For specific aim 2, hamstring muscle function of the injured leg was measured and compared to the contralateral leg using isometric hamstring force at 30, 60, and 90 degrees of knee flexion at 6 weeks and 6 months. Data are expressed as a Limb Symmetry Index (LSI), which is the percent force of the injured hamstring compared to the force of the non-injured hamstring muscle.	6 weeks; 6 months
Recovery of Hamstring Structure	For specific aim 2, recovery of hamstring structure was measured as the length of injury at 6 months as well as the change in proximal-distal length of injury from baseline to 6 month post-treatment MRI. Greater change in length represents greater healing.	6 months
Recovery of Hamstring Structure	For specific aim 2, hamstring structure was measured in terms of the volume of fibrosis at 6 month MRI, as such smaller volume of fibrosis represents greater healing of the hamstring muscle. Hamstring structure was also determined by comparing the change of pre-treatment volume of the injury on the baseline MRI to the volume of fibrosis on the 6 month MRI.	6 months
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. This could have occurred at any timepoint after 6 weeks, so this did not necessarily occur at 12 months but it was monitored until the 12 month timepoint.	12 months
Recurrence of Injury	Number of recurrent injuries will be monitored during the duration of the subjects participation.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of Hamstring Structure	For specific aim 2, restoration of hamstring structure was operationally defined as the ratio of the volume of the injured to contralateral leg hamstring volume 6 months after injury 6 months post-injury. The percent of hamstring volume of the injured leg was expressed as a percentage of the hamstring volume of the contralateral normal leg. The difference in volume between the involved and non-involved hamstring muscles was divided by the non-involved hamstring muscle volume and multiplied by 100.	6 months
Return to Prior Level of Function	For specific aims 3 and 4, return to prior level of sports activity was measured by the Marx Activity Scale Score, which ranges from 0 to 16, with 16 being the highest level of sports activity. The frequency of participants who achieved the same or better Marx score at follow-up compared to baseline was calculated. Differences from baseline to each follow-up timepoint were calculated by subtracting the follow-up scores from baseline. Any difference of 0 or a negative number indicated the participants achieved the same level of sports activity or better. Positive differences indicated they did not return to their prior level of sports activity.	4 Weeks, 6 Weeks, 3 Months, 4 Months, 6 Months, 12 Months
Recovery of Hamstring Flexibility	For specific aim 2, hamstring muscle flexibility of the injured leg was measured and compared to the contralateral leg using the popliteal angle at 6 weeks and 6 months after randomization. The popliteal angle was measured with a goniometer. Recovery of hamstring flexibility was operationally defined as the difference in the popliteal angle between the contralateral normal leg minus the hamstring injured leg. Positive differences between the contralateral and injured leg indicated decreased hamstring flexibility.	6 weeks; 6 months
Recovery of Hamstring Muscle Function	For specific aim 2, hamstring muscle function of the injured leg was measured and compared to the contralateral leg using isometric hamstring force at 1 week, 2 weeks, 3 weeks, and 4 weeks. Data were expressed as a Limb Symmetry Index (LSI), which is the percent strength of the injured hamstring in comparison to the strength of the non-injured hamstring muscle.	1 week; 2 weeks; 3 week; 4 weeks
Recovery of Hamstring Muscle Function	For specific aim 2, hamstring muscle function of the injured leg was measured on the Biodex and compared to the contralateral leg using isokinetic peak torque at 60 degrees and 180 degrees per second at 6 weeks and 6 months. Data were expressed as a Limb Symmetry Index (LSI), which is the percent peak torque of the injured hamstring compared to the peak torque of the non-injured hamstring muscle. The isokinetic testing was not consistently collected, so there are limited results to present at 6 months.	6 weeks, 6 months
Recovery of Hamstring Muscle Function	For specific aim 2, hamstring muscle function of the injured leg was measured on the Biodex and compared to the contralateral leg using isokinetic total hamstring work at 60 degrees per second and 180 degrees per second at 6 weeks and 6 months. Data were expressed as a Limb Symmetry Index (LSI), which is the percent total work of the injured hamstring compared to the total work of the non-injured hamstring muscle. The isokinetic testing was not consistently collected, so there are limited results to present at 6 months.	6 weeks, 6 months
Recovery of Hamstring Muscle Function	For specific aim 2, the ratio of hamstring peak torque to quadriceps peak torque at 60 degrees per second of the injured and non-injured legs were measured on the Biodex at 6 weeks. The isokinetic testing was not consistently collected, so there are limited results to present at 6 months.	6 weeks, 6 months
Recovery of Hamstring Muscle Function	For specific aim 2, the ratio of hamstring work in the last 3 repetitions to work in the first 3 repetitions at 180 degrees per second of the injured leg was measured on the Biodex at 6 weeks. The isokinetic testing was not consistently collected, so there are no results to present at 6 months.	6 weeks, 6 months

Collaborators and Investigators

• Sponsor: James J. Irrgang
• Collaborators: Brooke Army Medical Center; Wake Forest University
• Investigators: Principal Investigator: James J Irrgang, PT, PhD, University of Pittsburgh

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 (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

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)