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

NCT02263729 | Terminated Phase 1 Results

• 2 other identifiers: STUDY19100320W81XWH-14-2-0003
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Hamstring Injury

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (8)

• Recovery of Hamstring Structure

  6 months

• Return to Prior Level of Function

  4 Weeks, 6 Weeks, 3 Months, 4 Months, 6 Months, 12 Months

• Recovery of Hamstring Flexibility

  6 weeks; 6 months

• Recovery of Hamstring Muscle Function

  1 week; 2 weeks; 3 week; 4 weeks

• Recovery of Hamstring Muscle Function

  6 weeks, 6 months

Study Arms (2)

Losartan

ACTIVE COMPARATOR

Subjects will taken 50mg of losartan per day for 4 weeks

Drug: Losartan

Placebo

PLACEBO COMPARATOR

Subjects will be given placebo to replicate appearance of losartan pills. Placebo pill will be taken once per day.

Drug: Placebo

Interventions

Losartan DRUG

Cozaar

Losartan

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age and older;
• Have had grade II or III hamstring injury within the 7 days prior to enrollment;
• 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;
• Agree to take study medications as prescribed

You may not qualify if:

• 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;

Sponsors & Collaborators

• James J. Irrgang: lead
• Brooke Army Medical Center: collaborator
• Wake Forest University: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Interventions

Losartan

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Limitations and Caveats

Recruitment was complicated primarily due to delays in identifying potential study participants, as individuals were often excluded for presenting \> 7 days from injury (n=106), not having at least a grade 2 injury (n=9), or refusing participation (n=9). The study was terminated due to the expiration of funding, which resulted in a sample size of 6 participants. Given this sample size was smaller than anticipated, no between-group significance testing was performed.

Results Point of Contact

• Title: James J. Irrgang
• Organization: University of Pittsburgh

jirrgang@pitt.edu

412-383-9865

Study Officials

• James J Irrgang, PT, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PT, PhD

Study Record Dates

• First Submitted: September 26, 2014
• First Posted: October 13, 2014
• Study Start: August 10, 2016
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-04

Locations

US (1)