Effects of RLIC on Motor Learning in Middle-aged and Older Adults

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT03582943
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 82
• Location: 1
• Arms: 2
• Actual Duration (Months): 23.4
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

The purpose of this research is to determine if the beneficial effects of remote limb ischemic conditioning on learning seen in young adults are found in middle-aged and older adults.

Condition or Disease	Intervention/Treatment	Phase
Adults; Older Adults	Behavioral: RLIC; Behavioral: Sham conditioning; Behavioral: Balance training	Phase 1

Detailed Description

Ischemic conditioning is an endogenous phenomenon in which exposing a target organ or tissue to one or more brief episodes of ischemia results in protection of that organ against subsequent ischemia. The effects of ischemic conditioning are not confined within an organ but can be can be transferred from one organ to another, a technique called remote ischemic conditioning. A clinically feasible method for this is remote limb ischemic conditioning (RLIC), where episodes of ischemia and perfusion are induced with a blood pressure cuff placed on the arm.

The overall goal of this line of work is to use ischemic conditioning to enhance learning and outcomes in persons with neurologic injuries. Two previous studies have shown that remote limb ischemic conditioning (RLIC) can enhance learning a motor task in healthy young adults. The next step is to determine which individuals would receive maximum benefit from RLIC before applying these findings to clinical rehabilitation populations such as stroke. Numerous factors, such as age, body mass index (BMI), sex, and cardiovascular comorbidities may influence the response. The current study determines if RLIC can enhance learning in middle-aged and older adults with their burden of co-morbidities.

Study Design

• Study Type: Interventional
• Actual Enrollment: 82 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Single blinded, randomized, controlled trialSingle blinded, randomized, controlled trial
• Masking: Single (Participant)
• Masking Description: Participants are masked to their group assignment.
• Primary Purpose: Treatment
• Official Title: Effects of Remote Limb Ischemic Conditioning on Motor Learning in Middle-aged and Older Adults
• Actual Study Start Date: Oct 20, 2015
• Actual Primary Completion Date: Sep 15, 2017
• Actual Study Completion Date: Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Remote limb ischemic conditioning (RLIC) RLIC is achieved via blood pressure cuff inflation to 20 mmHg above systolic blood pressure on the dominant arm. RLIC requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. RLIC is performed on visits 1-7.	Behavioral: RLIC; See descriptions under arm/group descriptions. RLIC is delivered for 7 visits, occurring on consecutive weekdays.; Behavioral: Balance training; All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.
Sham Comparator: Sham conditioning Sham conditioning is achieved via blood pressure cuff inflation to 10 mmHg under diastolic blood pressure on the dominant arm. Sham conditioning requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. Sham conditioning is performed on visits 1-7.	Behavioral: Sham conditioning; See descriptions under arm/group descriptions. Sham conditioning is delivered for 7 visits, occurring on consecutive weekdays.; Behavioral: Balance training; All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.

Outcome Measures

Primary Outcome Measures

1. Change in Balance Score [1 week]

   Balance score at the end of training - balance score at baseline, where balance score is the average amount of time in seconds that a participant maintains the stability platform within ±3° of horizontal position during 5 trials of 30 seconds each. Five trials are averaged to form the balance score at each time point.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 40-80 years old

2. Had sufficient cognitive skills to provide informed consent and actively participate.

Exclusion Criteria (determined by self-report):

1. History of a neurological condition, balance impairment, or vestibular disorder.

2. History of attentional disorders (ADD/ADHD) that could affect learning.

3. History of sleep apnea which could confound the effects of RLIC.

4. Presence of lower extremity condition, injury, or surgery that would compromise performance on the balance task.

5. Learning disability, sensory, or communication problem that would prevent completion of the study.

6. History of epilepsy, peripheral vascular disease, or blood diathesis which could contraindicate RLIC.

7. Current intensive weight lifting or interval training exercise which could confound the effects of RLIC.

8. Current substance abuse or dependence.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63108

Sponsors and Collaborators

• Washington University School of Medicine
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Catherine Lang, PT, PhD, Washington University School of Medicine

Study Documents (Full-Text)

• Informed Consent Form - Oct 30, 2017
• Study Protocol and Statistical Analysis Plan - Jun 20, 2016

More Information

Publications

None provided.

• Responsible Party: Catherine E. Lang, Professor, Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03582943
• Other Study ID Numbers: NIHR01HD085930-Aim3; R01HD085930
• First Posted: Jul 11, 2018
• Last Update Posted: Oct 24, 2018
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Catherine E. Lang, Professor, Washington University School of Medicine: remote ischemic conditioning, motor learning

Study Results

Participant Flow

Recruitment Details	Participants recruited by word-of-mouth and through participant registry. Assessed for eligibility, n = 182. Excluded, n = 100 with n = 33 not meeting criteria, n = 64 declined to participate, and n = 3 pilot participants who were not randomized.

Arm/Group Title	Remote Limb Ischemic Conditioning (RLIC)	Sham Conditioning
Arm/Group Description	RLIC is achieved via blood pressure cuff inflation to 20 mmHg above systolic blood pressure on the dominant arm. RLIC requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. RLIC is performed on visits 1-7. RLIC: See descriptions under arm/group descriptions. RLIC is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.	Sham conditioning is achieved via blood pressure cuff inflation to 10 mmHg under diastolic blood pressure on the dominant arm. Sham conditioning requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. Sham conditioning is performed on visits 1-7. Sham conditioning: See descriptions under arm/group descriptions. Sham conditioning is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.
Period Title: Allocated to Groups
STARTED	42	40
COMPLETED	41	39
NOT COMPLETED	1	1
Period Title: Allocated to Groups
STARTED	41	39
COMPLETED	37	37
NOT COMPLETED	4	2
Period Title: Allocated to Groups
STARTED	37	37
COMPLETED	33	36
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Remote Limb Ischemic Conditioning (RLIC)	Sham Conditioning	Total
Arm/Group Description	RLIC is achieved via blood pressure cuff inflation to 20 mmHg above systolic blood pressure on the dominant arm. RLIC requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. RLIC is performed on visits 1-7. RLIC: See descriptions under arm/group descriptions. RLIC is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.	Sham conditioning is achieved via blood pressure cuff inflation to 10 mmHg under diastolic blood pressure on the dominant arm. Sham conditioning requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. Sham conditioning is performed on visits 1-7. Sham conditioning: See descriptions under arm/group descriptions. Sham conditioning is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.	Total of all reporting groups
Overall Participants	33	36	69
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (10.5)	61.8 (9.0)	61.2 (10.0)
Sex: Female, Male (Count of Participants)
Female	22 66.7%	25 69.4%	47 68.1%
Male	11 33.3%	11 30.6%	22 31.9%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	25 75.8%	26 72.2%	51 73.9%
African-American	8 24.2%	10 27.8%	18 26.1%
Region of Enrollment (Count of Participants)
United States	33 100%	36 100%	69 100%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.5 (4.4)	26.8 (5.1)	26.6 (4.8)

Outcome Measures

1. Primary Outcome

Title	Change in Balance Score
Description	Balance score at the end of training - balance score at baseline, where balance score is the average amount of time in seconds that a participant maintains the stability platform within ±3° of horizontal position during 5 trials of 30 seconds each. Five trials are averaged to form the balance score at each time point.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

Only participants who completed the entire protocol and did not have a protocol deviation were analyzed.

Arm/Group Title	Remote Limb Ischemic Conditioning (RLIC)	Sham Conditioning
Arm/Group Description	RLIC is achieved via blood pressure cuff inflation to 20 mmHg above systolic blood pressure on the dominant arm. RLIC requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. RLIC is performed on visits 1-7. RLIC: See descriptions under arm/group descriptions. RLIC is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.	Sham conditioning is achieved via blood pressure cuff inflation to 10 mmHg under diastolic blood pressure on the dominant arm. Sham conditioning requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. Sham conditioning is performed on visits 1-7. Sham conditioning: See descriptions under arm/group descriptions. Sham conditioning is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.
Measure Participants	33	36
Mean (Standard Deviation) [seconds]	5.55 (4.85)	4.81 (3.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Remote Limb Ischemic Conditioning (RLIC), Sham Conditioning
	Comments
	Type of Statistical Test	Superiority
	Comments	A priori power analyses was designed to detect at least a 3 second difference in change in balance scores between groups.
Statistical Test of Hypothesis	p-Value	0.984
	Comments	Test of differences between groups.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Remote Limb Ischemic Conditioning (RLIC), Sham Conditioning
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.455
	Comments	Test of interaction between age and RLIC vs. sham
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.023
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Remote Limb Ischemic Conditioning (RLIC), Sham Conditioning
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.803
	Comments	Test of interaction between sex and RLIC vs. sham conditioning
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Remote Limb Ischemic Conditioning (RLIC), Sham Conditioning
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.233
	Comments	Test of interaction between BMI and RLIC vs. sham conditioning
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.25
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Remote Limb Ischemic Conditioning (RLIC), Sham Conditioning
	Comments
	Type of Statistical Test	Superiority
	Comments	Test of interaction between presence of co-morbidities and RLIC vs. sham conditioning
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.12
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	From enrollment through follow-up for a total of 6 weeks
Arm/Group Title	Remote Limb Ischemic Conditioning (RLIC)		Sham Conditioning
Arm/Group Description	RLIC is achieved via blood pressure cuff inflation to 20 mmHg above systolic blood pressure on the dominant arm. RLIC requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. RLIC is performed on visits 1-7. RLIC: See descriptions under arm/group descriptions. RLIC is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.		Sham conditioning is achieved via blood pressure cuff inflation to 10 mmHg under diastolic blood pressure on the dominant arm. Sham conditioning requires 45 minutes and involves 5 cycles of 5 minutes blood pressure cuff inflation followed by alternating 5 minutes of cuff deflation. Sham conditioning is performed on visits 1-7. Sham conditioning: See descriptions under arm/group descriptions. Sham conditioning is delivered for 7 visits, occurring on consecutive weekdays. Balance training: All participants undergo training on a balance board, learning to hold the board level with equal weight on each leg. This is a motor learning task. Participants perform the balance task for 15, 30-second trials per day at visits 3-7.
All Cause Mortality
	Remote Limb Ischemic Conditioning (RLIC)		Sham Conditioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/36 (0%)
Serious Adverse Events
	Remote Limb Ischemic Conditioning (RLIC)		Sham Conditioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Remote Limb Ischemic Conditioning (RLIC)		Sham Conditioning
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/33 (0%)		0/36 (0%)

Limitations/Caveats

This was a Phase I study in a small sample.

More Information

Certain Agreements

All Principal Investigators ARE 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.