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

Phase 1

Terminated

Conditions: Hamstring Injury

Interventions: Drug: Placebo
Drug: Losartan

Registration Number: NCT02263729

Lead Sponsor: James J. Irrgang

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

Inclusion Criteria

Not provided

Exclusion Criteria

Have had previous hamstring injury on the same side or chronic symptoms;
Have an injury that requires surgical intervention (e.g. avulsion with associated bony involvement, grade III complete tears);
Have concurrent lower back symptoms;
Pregnant or breast feeding;
Is a smoker;
Has contraindications for Losartan therapy (hypersensitivity to Losartan, hepatic involvement);
Currently use angiotensin I converting enzyme inhibitor (ACEI)/ Angiotensin II receptor blocker (ARB);
Have hypertension (blood pressure greater than or equal to 140 mmHg systolic pressure or greater than or equal to 90 mmHg diastolic pressure);
Have hypotension (blood pressure less than or equal to 90 mmHg systolic pressure or less than or equal to 60 mmHg diastolic pressure);
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;
Have diabetes mellitus, cardiovascular, renal or hepatic co-morbidities;
Sickle cell anemia/trait;
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects will be given placebo to replicate appearance of losartan pills. Placebo pill will be taken once per day.
Losartan	Losartan	Subjects will taken 50mg of losartan per day for 4 weeks

Primary Outcome Measures

Name	Time	Method
Recovery of Hamstring Structure	6 months	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.
Recovery of Hamstring Muscle Function	6 weeks; 6 months	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.
Return to Prior Level of Function	12 months	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.
Reported Effects of Losartan for Hamstring Injury for Safety and Tolerability	4 weeks	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.
Recurrence of Injury	12 months	Number of recurrent injuries will be monitored during the duration of the subjects participation.

Secondary Outcome Measures

Name	Time	Method
Recovery of Hamstring Structure	6 months	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.
Return to Prior Level of Function	4 Weeks, 6 Weeks, 3 Months, 4 Months, 6 Months, 12 Months	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.
Recovery of Hamstring Flexibility	6 weeks; 6 months	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.
Recovery of Hamstring Muscle Function	6 weeks, 6 months	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.