Electrical Stimulation and Eccentric Exercise for Anterior Cruciate Ligament (ACL) Injury

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT01555567
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH)
• Enrollment: 43
• Location: 1
• Arms: 4
• Duration (Months): 59
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

Quadriceps muscle weakness is a common consequence of ACL injury. This muscle weakness is considered to result from neural inhibition preventing full muscle contraction and is referred to as arthrogenic muscle inhibition (AMI). AMI hinders rehabilitation by preventing gains in strength, increasing the risk of re-injury, and potentially placing patients at risk for chronic degenerative joint conditions. Quadriceps weakness that occurs following ACL injury is also thought to be caused by muscle atrophy which is thought to manifest due to alterations in muscle architecture, selective fiber atrophy or even neural deficits such as AMI. Importantly, interventions that are designed to counter this muscle weakness are required in order to promote long-term knee joint health. Hence, the purpose of the current study is to determine the efficacy of interventions that target quadriceps weakness to improve quadriceps muscle function and biomechanics in patients prior to and following ACL reconstruction. Specifically, the efficacy of neuromuscular electrical stimulation aimed at improving quadriceps neural activity and eccentric exercise intended to minimize quadriceps muscle atrophy will be investigated. The investigators expect that patients who receive the electrical stimulation therapy will demonstrate improvements in quadriceps strength and activation. Furthermore, it is expected that patients who receive both the electrical stimulation and eccentric intervention will demonstrate markedly greater gains in quadriceps strength and activation than patients who receive only the electrical stimulation therapy or standard of care post-surgery. The investigators also hypothesize that the patients who receive the electrical stimulation therapy and/or eccentrics will display knee motion similar to uninjured control subjects.

Condition or Disease	Intervention/Treatment	Phase
Anterior Cruciate Ligament Injury	Device: Electrical Stimulation; Other: Eccentric Exercise	N/A

Detailed Description

Neuromuscular electrical stimulation (NMES) has been shown to reduce quadriceps activation failure (QAF) and eccentric exercise has been shown to lessen muscle atrophy post-ACL reconstruction. Given thatthese are two critical components of quadriceps strength, intervention combining these therapies may be effective at reinstituting quadriceps function post-reconstruction. Therefore, the aim of this study is to evaluate the effectiveness of a combined NMES and eccentric exercise intervention to improve the recovery of quadriceps activation and strength post-reconstruction. Patients post ACL-injury will be placed into four treatment groups (NMES and eccentrics; eccentrics only; NMES only, and standard of care) Patients assigned to the NMES and eccentric and the NMES only groups will receive the NMES protocol 2× per week for the first 6 weeks post-reconstruction. MES and eccentric and the eccentrics only groups will receive the eccentric exercise protocol 2× perweek beginning 6 weeks post-reconstruction. Quadriceps activation was assessed via the superimposed burst technique and quantified via the central activation ratio.Quadriceps strength was assessed via maximal voluntary isomeric contractions (Nm/kg). Data will be gathered on three occasions: pre-operative, 12-weeks-post-surgery and at return-to-play.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Quadriceps Inhibition After ACL Injury: Neuromuscular and Functional Consequences
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: Jul 1, 2014
• Actual Study Completion Date: Jul 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Electrical stimulation Subjects placed into this group will undergo electrical stimulation following anterior cruciate ligament reconstruction (ACLr). Subjects will be required to report 2 times per week for 6 weeks following ACLr for electrical stimulation therapy. Electrical stimulation therapy post-reconstruction will commence immediately post-ACLr and end at week 6.	Device: Electrical Stimulation; Electrical stimulation will be delivered 2 times per week
No Intervention: Standard of Care This group will undergo standard ACL rehabilitation
Experimental: Eccentric Exercise Subjects placed into this group will undergo eccentric exercise strength training following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr. Eccentric strengthening will begin at week 6 post-ACLr and will end at week 12 post-ACLr.	Other: Eccentric Exercise; Eccentric Exercise will be delivered 2 times per week
Experimental: Stimulation and Eccentrics Subjects placed into this group will undergo a combined electrical stimulation and eccentric exercise intervention following ACLr. The electrical stimulation intervention will be delivered immediately following ACLr and will end at 6 weeks post-ACLr. Subjects will receive the electrical stimulation therapy 2 times per week for the first 6 weeks post-ACLr. At six weeks post-ACLr, subjects will begin the eccentric strengthening protocol. Subjects will eccentrically train 2 times per week for 6 weeks. The eccentric strengthening will end at 12 weeks post-ACLr.	Device: Electrical Stimulation; Electrical stimulation will be delivered 2 times per week; Other: Eccentric Exercise; Eccentric Exercise will be delivered 2 times per week

Outcome Measures

Primary Outcome Measures

1. Quadriceps Strength [Time of return to activity (~6 months following surgery)]

Secondary Outcome Measures

1. Central Activation Ratio [Time of return to activity (~6 months following surgery)]

   CAR = maximal voluntary isometric contractions force / maximal voluntary isometric contractions force + stimulated force

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years to 35 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Aged 14-35 years

• Willingness to participate in testing and follow-up as outlined in the protocol

• Scheduled to undergo ACL reconstruction

Exclusion Criteria:

• Previous quadriceps injury

• Inability to provide informed consent

• Pregnant females

• ACL injury sustained more than 48 hours prior to reporting to physician

• ACL injury sustained when not engaged in sports participation (i.e. while engaged in activities of daily living)

• Previous partial ACL tear

• Previous surgery to injured knee

• Total or partial meniscectomy accompanying ACL reconstruction

• Other ligamentous injury accompanying ACL injury

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MedSport	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Riann M Palmieri-Smith, PhD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Riann Palmieri-Smith, Associate Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT01555567
• Other Study ID Numbers: ACLNMES; 1K08AR053152-01A2
• First Posted: Mar 15, 2012
• Last Update Posted: Jun 8, 2015
• Last Verified: May 1, 2015

• Keywords provided by Riann Palmieri-Smith, Associate Professor, University of Michigan: ACL; muscle; quadriceps; strength
• Additional relevant MeSH terms: Wounds and Injuries; Anterior Cruciate Ligament Injuries

Study Results

Participant Flow

Arm/Group Title	Neuromuscular Electrical Stimulation	Standard of Care	Eccentric Exercise	Combination of NMES and Eccentric Exercise
Arm/Group Description	Subjects placed into this group will undergo neuromuscular electrical stimulation (NMES) following anterior cruciate ligament (ACLr). Subjects will be required to report 2 times per week for 6 weeks following ACLr for NMES therapy. NMES therapy post-reconstruction will commence immediately post-ACLr and end at week 6. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week	This group will undergo standard ACL rehabilitation	Subjects placed into this group will undergo eccentric exercise strength training following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr. Eccentric strengthening will begin at week 6 post-ACLr and will end at week 12 post-ACLr. Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week	Subjects placed into this group will undergo a combined NMES and eccentric exercise intervention following ACLr. The NMES intervention will be delivered immediately following ACLr and will end at 6 weeks post-ACLr. Subjects will receive the NMES therapy 2 times per week for the first 6 weeks post-ACLr. At six weeks post-ACLr, subjects will begin the eccentric strengthening protocol. Subjects will eccentrically train 2 times per week for 6 weeks. The eccentric strengthening will end at 12 weeks post-ACLr. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week
Period Title: 12 Week
STARTED	12	13	9	9
COMPLETED	11	12	8	9
NOT COMPLETED	1	1	1	0
Period Title: 12 Week
STARTED	11	12	8	9
COMPLETED	10	10	8	8
NOT COMPLETED	1	2	0	1

Baseline Characteristics

Arm/Group Title	Neuromuscular Electrical Stimulation	Standard of Care	Eccentric Exercise	Combination of NMES and Eccentric Exercise	Total
Arm/Group Description	Subjects placed into this group will undergo NMES following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr for NMES therapy. NMES therapy post-reconstruction will commence immediately post-ACLr and end at week 6. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week	This group will undergo standard ACL rehabilitation	Subjects placed into this group will undergo eccentric exercise strength training following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr. Eccentric strengthening will begin at week 6 post-ACLr and will end at week 12 post-ACLr. Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week	Subjects placed into this group will undergo a combined NMES and eccentric exercise intervention following ACLr. The NMES intervention will be delivered immediately following ACLr and will end at 6 weeks post-ACLr. Subjects will receive the NMES therapy 2 times per week for the first 6 weeks post-ACLr. At six weeks post-ACLr, subjects will begin the eccentric strengthening protocol. Subjects will eccentrically train 2 times per week for 6 weeks. The eccentric strengthening will end at 12 weeks post-ACLr. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week	Total of all reporting groups
Overall Participants	10	10	8	8	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.8 (4.4)	18.3 (3.7)	23.2 (5.4)	23.2 (6.3)	21.6 (4.9)
Sex: Female, Male (Count of Participants)
Female	2 20%	5 50%	3 37.5%	3 37.5%	13 36.1%
Male	8 80%	5 50%	5 62.5%	5 62.5%	23 63.9%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	8 100%	8 100%	36 100%
Height (meter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [meter]	1.76 (.1)	1.73 (.1)	1.75 (.1)	1.45 (.6)	1.67 (.22)
Mass (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	81.65 (22.6)	75.5 (24.1)	77.7 (10.4)	77.8 (16.5)	78.2 (18.4)
Quadriceps Strength (Nm/kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Nm/kg]	2.6 (.6)	2.6 (.6)	2.8 (1.1)	2.7 (.8)	2.67 (.78)
Central Activation Ratio (CAR) (ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ratio]	97.4 (3)	94.9 (5.3)	95.9 (4.5)	95.7 (3.5)	95.9 (4.1)

Outcome Measures

1. Primary Outcome

Title	Quadriceps Strength
Time Frame	Time of return to activity (~6 months following surgery)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neuromuscular Electrical Stimulation	Standard of Care	Eccentric Exercise	Combination of NMES and Eccentric Exercise
Arm/Group Description	Subjects placed into this group will undergo NMES following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr for NMES therapy. NMES therapy post-reconstruction will commence immediately post-ACLr and end at week 6. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week	This group will undergo standard ACL rehabilitation	Subjects placed into this group will undergo eccentric exercise strength training following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr. Eccentric strengthening will begin at week 6 post-ACLr and will end at week 12 post-ACLr. Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week	Subjects placed into this group will undergo a combined NMES and eccentric exercise intervention following ACLr. The NMES intervention will be delivered immediately following ACLr and will end at 6 weeks post-ACLr. Subjects will receive the NMES therapy 2 times per week for the first 6 weeks post-ACLr. At six weeks post-ACLr, subjects will begin the eccentric strengthening protocol. Subjects will eccentrically train 2 times per week for 6 weeks. The eccentric strengthening will end at 12 weeks post-ACLr. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week
Measure Participants	10	10	8	8
Mean (Standard Deviation) [Nm/kg]	2.1 (0.6)	2.1 (0.6)	2.8 (0.9)	2.9 (0.6)

2. Secondary Outcome

Title	Central Activation Ratio
Description	CAR = maximal voluntary isometric contractions force / maximal voluntary isometric contractions force + stimulated force
Time Frame	Time of return to activity (~6 months following surgery)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Neuromuscular Electrical Stimulation	Standard of Care	Eccentric Exercise	Combination of NMES and Eccentric Exercise
Arm/Group Description	Subjects placed into this group will undergo NMES following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr for NMES therapy. NMES therapy post-reconstruction will commence immediately post-ACLr and end at week 6. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week	This group will undergo standard ACL rehabilitation	Subjects placed into this group will undergo eccentric exercise strength training following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr. Eccentric strengthening will begin at week 6 post-ACLr and will end at week 12 post-ACLr. Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week	Subjects placed into this group will undergo a combined NMES and eccentric exercise intervention following ACLr. The NMES intervention will be delivered immediately following ACLr and will end at 6 weeks post-ACLr. Subjects will receive the NMES therapy 2 times per week for the first 6 weeks post-ACLr. At six weeks post-ACLr, subjects will begin the eccentric strengthening protocol. Subjects will eccentrically train 2 times per week for 6 weeks. The eccentric strengthening will end at 12 weeks post-ACLr. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week
Measure Participants	10	10	8	8
Mean (Standard Deviation) [ratio]	91.8 (4.6)	91.8 (9)	98.1 (1.2)	97.6 (2.8)

Adverse Events

Arm/Group Title	Neuromuscular Electrical Stimulation		Standard of Care		Eccentric Exercise		Combination of NMES and Eccentric Exercise
Arm/Group Description	Subjects placed into this group will undergo NMES following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr for NMES therapy. NMES therapy post-reconstruction will commence immediately post-ACLr and end at week 6. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week		This group will undergo standard ACL rehabilitation		Subjects placed into this group will undergo eccentric exercise strength training following ACLr. Subjects will be required to report 2 times per week for 6 weeks following ACLr. Eccentric strengthening will begin at week 6 post-ACLr and will end at week 12 post-ACLr. Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week		Subjects placed into this group will undergo a combined NMES and eccentric exercise intervention following ACLr. The NMES intervention will be delivered immediately following ACLr and will end at 6 weeks post-ACLr. Subjects will receive the NMES therapy 2 times per week for the first 6 weeks post-ACLr. At six weeks post-ACLr, subjects will begin the eccentric strengthening protocol. Subjects will eccentrically train 2 times per week for 6 weeks. The eccentric strengthening will end at 12 weeks post-ACLr. Neuromuscular Electrical Stimulation: NMES will be delivered 2 times per week Eccentric Exercise: Eccentric Exercise will be delivered 2 times per week
All Cause Mortality
	Neuromuscular Electrical Stimulation		Standard of Care		Eccentric Exercise		Combination of NMES and Eccentric Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Neuromuscular Electrical Stimulation		Standard of Care		Eccentric Exercise		Combination of NMES and Eccentric Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Neuromuscular Electrical Stimulation		Standard of Care		Eccentric Exercise		Combination of NMES and Eccentric Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/8 (0%)		0/8 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.