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SCI: Lipid Abnormalities (2007)

Citation:

Stewart BG, Tarnopolsky MA, Hicks AL, McCartney N, Mahoney DJ, Staron RS, Phillips SM. Treadmill training-induced adaptations in muscle phenotype in persons with incomplete spinal cord injury. Muscle Nerve. 2004; 30(1): 61-68.

PubMed ID: 15221880
 
Study Design:
Longitudinal prospective study design.
Class:
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

The researchers aimed to determine if six months (three sessions per week) of body-weight supported treadmill (BWST) training in neurologically stable persons with a traumatic spinal cord injury (ASIA C) alters skeletal muscle phenotype, ambulatory capacity and blood lipid profile. 

Inclusion Criteria:
  • Neurologically stable patients with a traumatic spinal cord injury of an incomplete lesion ranging between C4 and T12
  • Utilize a wheelchair exclusively for daily activities
  • Not actively engaged in any form of exercise training and not regularly participating in any form of structured physical activity at the time of the BWST training protocol. 
Exclusion Criteria:
  • Evidence or past history of ischemic heart disease, unstable angina, cardiac dysrhythmia or autonomic dysreflexia, recent osteoporotic fracture or tracheotomy
  • Subjects actively engaged in physical activity.
Description of Study Protocol:

Recruitment

All subjects were recruited through local advertisements in newspapers and by contact with medical staff at the Central Ontario, West Regional SCI Rehabilitation Program (Chedoke Hospital, Hamilton, Ontario), where some subjects were receiving periodic standard outpatient rehabilitative treatment. 

Design

  • A longitudinal prospective study design was utilized with subjects being evaluated both pre- and post-training through muscle biopsies or pre-, mid- and post-training (treadmill walking data)
  • The study spanned 68 exercise sessions (2.8±0.2 training sessions a week) and took 6.0±0.3 months for the subjects to complete
  • All subjects completed 68 training sessions, which were designed to encompass three training sessions per week
  • Some subjects missed some training sessions due to reasons unrelated to the study, but no subject missed more than one training session in any given week.

Intervention

  • Subjects began training upright walking on a motor-driven treadmill
  • Training was begun with 65%±3% of their body weight supported and walked at a treadmill speed of less than 0.6km per hour.

Statistical Analysis

  •  Data was analyzed using repeated-measures one-way analysis of variance (ANOVA) for treadmill walking (velocity, time, body weight-supported) with three levels: pre-training; following three months of training; and following six months of training, Fiber type (I, IIa, IIax +IIx) data (CSA, percent distribution, percent area) were analyzed for ANOVA, with fiber type (I, IIa, IIax + IIx) and time (pre- and post-training) as factors
  • Most MHC data (I, IIa, and IIx) were analyzed using a two-way within-repeated-measures ANOVA, with time and percent of total as factors
  • Tukey post-hoc tests were used to compare means
  • Measures of blood lipids, enzyme activities and western blot analyses were analyzed using paired T-tests (pre- vs. post-training)
  • All correlations were determined using a Pearson product correlation coefficient
  • Significance was set at 5%
  • All data are presented as mean±SE.
Data Collection Summary:

Timing of Measurements

  • Subjects were evaluated both pre- and post-training through muscle biopsies or pre-, mid- and post-training (treadmill walking data)
  • The study spanned 68 exercise sessions (2.8±0.2 training sessions a week) and took 6.0±0.3 months for the subjects to complete.

Dependent Variables

  • Functional ambulatory capactity was assessed by the use of a six-item classification scale the delineartes between independent and dependent standing or walking, with or without ambulatory aides
  • Blood lipid profile was assessed through the collection of 12-hour fasting blood samples for total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides
  • Muscle fiber analysis were characterized according to their adenosine triphosphatase (ATPase) activity following acidic pH (4.56) pre-incubation
  • Enzyme activities were characterized by hand-homogenizing 10mg of muscle where the activity for each enzyme was calculated and expressed as micromoles per minute per gram of weight of muscle. 

Independent Variables

BWST training.

Description of Actual Data Sample:
  • Initial N: Nine
  • Attrition (final N): Nine
  • Age: 31+3 years of age.

Other Relevant Demographics

  • Eight men and one woman were recruited to participate in the study
  • Average time since injury was 8.1±2.5 (mean±SE) years
  • All subjects were neurologically stable
  • All lesions (C4 to T12) were incomplete
  • All subjects were classified as having an ASIA score of C
  • All subjects utilized wheelchairs exclusively for daily activities
  • No subject was actively engaged in any form of exercise training and was not regularly participating in any form of structured physical activity.

Anthropometrics

  • Subjects were 1.80±0.04 meters tall
  • Body mass index (BMI) was 23.3±1.1kg/m2.

Location

Hamilton, Ontario. 

Summary of Results:

Treadmill Performance and Functional Ambulation

  • BWST walking velocity and time per BWST increased following BWST training by 135% (P<0.01) and 55% (P<0.01) respectively 
  • The amount of body weight supported externally decreased significantly throughout the training program (pre-training, 65%±3%; three months, 41%±3% (P<0.05); and six months, 23%±5% (P<0.05 vs. three months). Four of the nine subjects also showed improvements in their functional locomotor capacity (S3, zero to four; S4, seven to eight; S5, zero to seven; S7, zero to two).

Blood Lipids

  • Following BWST training there were significant reductions in total cholesterol (total-C), LDL-C, and total-C, HDL-C
  • HDL and serum triglycerides were unchanged after the training.

Muscle Fiber Characteristics

  • The increase in mean fiber area for the groups as a whole was 25.5%±7.3% (P<0.001)
  • The increase in Type IIa fiber percentage was accompanied by a decrease in type IIa or IIx fibers, which comprised 49.7%±6.0 % of all fibers pre-training and 36.0%±4.0% of all fibers post-training (P<0.05)
  • The percentage of fibers that were type I remained unchanged (pre-training, 18.7%±5.0%; post-training, 22%±5.0% ( P=0.41).

MHC

  • There was a significant 24%±5% reduction in the percentage of type IIx MHC (P<0.05)
  • No changes were seen for either type IIa or type I MHC abundance (Type IIa, P=0.16; Type I, P=0.26).

Enzymes

  • BWST training induced increases in both maximal CS activity and CS abundance as determined by western blot 
  • The increase in CS was seen in all subjects and represented a mean 39%±8% increase in activity from pre-training (P<0.01)
  • The overall abundance of CS increased following BWST training in all nine subjects (mean increase, 74%±16%; P<0.01).
Author Conclusion:

In patients with spinal cord injury, BWST is able to induce an increase in muscle fiber and bring about increases in muscle oxidative capacity. In addition, BWST training can bring about improvements in ambulatory capacity and anti-atherogenic changes in blood lipid profile. 

Funding Source:
Reviewer Comments:

This research used an extremely small (N=9) sample size.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? N/A
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? Yes
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? No
  10.2. Was the study free from apparent conflict of interest? Yes