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

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.

Time frame: 6 weeks; 6 months

Population: Losartan Group: 4 wk data at 30 \& 90 degrees substituted for 6 wk data (1 subject lost to follow-up at 4 wks, 1 data not collected). 6 wk data at 60 degrees missing for subject lost to follow-up at 4 wks. 6 m data missing for subject lost to follow-up at 4 wks \& not collected for 1 subject Placebo group: 6 wk data at 60 degrees not collected for 1 participant. 6 m data missing for 1 subject that moved out of the area prior to 6 m \& data not collected for 1 subject at 60 degrees of flexion

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.

Time frame: 6 months

Population: Losartan group: one participant was completely lost to follow-up after 4 weeks. There is also missing MRI data for 6-month timepoint for one other participant.~Placebo group: one participant moved out of the area before the 6-month visit and did not complete the 6 month clinical research visit.

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.

Time frame: 6 months

Population: Losartan group: one participant was completely lost to follow-up after 4 weeks. There is also missing MRI data for 6-month timepoint for one other participant.~Placebo group: one participant moved out of the area before the 6-month visit and did not complete the clinical research visit.

Number of recurrent injuries will be monitored during the duration of the subjects participation.

Time frame: 12 months

Population: Losartan group: one participant was completely lost to follow-up after 4 weeks. Placebo group: one participant moved out of the area before the 6-month visit and did not complete the clinical assessment portion, however reinjury reporting was tracked until 9 months, after which the individual was lost to further follow-up.

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.

Time frame: 4 weeks

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.

Time frame: 12 months

Population: Despite losing one participant in the Losartan group after 4 weeks and one in the placebo group after 9 months, data for this outcome was able to be collected and analyzed as the participants returned to their prior level of function before they were lost to follow-up.

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.

Time frame: 6 weeks; 6 months

Population: Losartan group: one participant was completely lost to follow-up after 4 weeks. Placebo group: one participant moved out of the area before the 6-month visit and did not complete the clinical research follow-up and then was completely lost to follow-up after the 9 month telephone call.

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.

Time frame: 6 weeks, 6 months

Population: Losartan group: At 6 weeks, one participant was completely lost to follow-up after 4 weeks, and another participant did not complete isokinetic testing.~Placebo group: At 6 weeks, data is missing for one participant, and another did not complete isokinetic testing.~Data was not collected at 6 months for either group.

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.

Time frame: 6 weeks, 6 months

Population: Losartan group: At 6 weeks, one participant was completely lost to follow-up after 4 weeks, and another participant did not complete isokinetic testing. At 6 months, data was collected for one participant, since one was lost to follow-up and the other did not complete isokinetic testing.~Placebo group: At 6 weeks, data is missing for one participant, and another did not complete isokinetic testing. At 6 months, data was not collected for this group.

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.

Time frame: 6 weeks, 6 months

Population: Losartan group: At 6 weeks, one participant was completely lost to follow-up after 4 weeks, and another participant did not complete isokinetic testing. At 6 months, data was collected for one participant, since one was lost to follow-up and the other did not complete isokinetic testing.~Placebo group: At 6 weeks, data is missing for one participant, and another did not complete isokinetic testing. At 6 months, data was not collected for this group.

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.

Time frame: 1 week; 2 weeks; 3 week; 4 weeks

Population: For the 4 week strength assessment, one participant in the Losartan group did not have isometric strength testing completed.

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.

Time frame: 6 weeks, 6 months

Population: Losartan group: At 6 weeks, one participant was completely lost to follow-up after 4 weeks, and another participant did not complete isokinetic testing. At 6 months, data was collected for one participant, since one was lost to follow-up and the other did not complete isokinetic testing.~Placebo group: At 6 weeks, data is missing for one participant, and another did not complete isokinetic testing. At 6 months, data was not collected for this group.

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.

Time frame: 6 months

Population: Losartan group: one participant was completely lost to follow-up after 4 weeks. There is also missing MRI data for 6-month timepoint for one other participant.~Placebo group: one participant moved out of the area before the 6-month visit and did not complete the clinical research follow-up visit and then was completely lost to follow-up after the 9 month telephone call.

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.

Time frame: 4 Weeks, 6 Weeks, 3 Months, 4 Months, 6 Months, 12 Months

Population: Losartan group: one participant was completely lost to follow-up after 4 weeks. Placebo group: one participant moved out of the area before the 6-month visit and did not complete the clinical assessment portion of the research follow-up, then was completely lost to follow-up after the 9 month telephone call.