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Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training.

ABSTRACT: Exercise promotes repair processes in the mouse brain and improves cognition in both mice and humans. It is not known whether these benefits translate to human brain injury, particularly the significant injury observed in children treated for brain tumors.We conducted a clinical trial with crossover of exercise training versus no training in a restricted sample of children treated with radiation for brain tumors. The primary outcome was change in brain structure using MRI measures of white matter (ie, fractional anisotropy [FA]) and hippocampal volume [mm3]). The secondary outcome was change in reaction time (RT)/accuracy across tests of attention, processing speed, and short-term memory. Linear mixed modeling was used to test the effects of time, training, training setting, and carryover.Twenty-eight participants completed training in either a group (n=16) or a combined group/home (n=12) setting. Training resulted in increased white matter FA (?=0.05, P<.001). A carryover effect was observed for participants ~12 weeks after training (?=0.05, P<.001). Training effects were observed for hippocampal volume (?=130.98mm3; P=.001) and mean RT (?=-457.04ms, P=0.36) but only in the group setting. Related carryover effects for hippocampal volume (?=222.81mm3, P=.001), and RT (?=-814.90ms, P=.005) were also observed. Decreased RT was predicted by increased FA (R=-0.62, P=.01). There were no changes in accuracy.Exercise training is an effective means for promoting white matter and hippocampal recovery and improving reaction time in children treated with cranial radiation for brain tumors.

SUBMITTER: Riggs L

PROVIDER: S-EPMC5464296 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training.

Riggs Lily L Piscione Janine J Laughlin Suzanne S Cunningham Todd T Timmons Brian W BW Courneya Kerry S KS Bartels Ute U Skocic Jovanka J de Medeiros Cynthia C Liu Fang F Persadie Nicholas N Scheinemann Katrin K Scantlebury Nadia N Szulc Kamila U KU Bouffet Eric E Mabbott Donald J DJ

Neuro-oncology 20170301 3

<h4>Background</h4>Exercise promotes repair processes in the mouse brain and improves cognition in both mice and humans. It is not known whether these benefits translate to human brain injury, particularly the significant injury observed in children treated for brain tumors.<h4>Methods</h4>We conducted a clinical trial with crossover of exercise training versus no training in a restricted sample of children treated with radiation for brain tumors. The primary outcome was change in brain structur ...[more]

PMID: 27555603

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Project description:We asked whether pharmacological stimulation of endogenous neural precursor cells (NPCs) may promote cognitive recovery and brain repair, focusing on the drug metformin, in parallel rodent and human studies of radiation injury. In the rodent cranial radiation model, we found that metformin enhanced the recovery of NPCs in the dentate gyrus, with sex-dependent effects on neurogenesis and cognition. A pilot double-blind, placebo-controlled crossover trial was conducted (ClinicalTrials.gov, NCT02040376) in survivors of pediatric brain tumors who had been treated with cranial radiation. Safety, feasibility, cognitive tests and MRI measures of white matter and the hippocampus were evaluated as endpoints. Twenty-four participants consented and were randomly assigned to complete 12-week cycles of metformin (A) and placebo (B) in either an AB or BA sequence with a 10-week washout period at crossover. Blood draws were conducted to monitor safety. Feasibility was assessed as recruitment rate, medication adherence and procedural adherence. Linear mixed modeling was used to examine cognitive and MRI outcomes as a function of cycle, sequence and treatment. We found no clinically relevant safety concerns and no serious adverse events associated with metformin. Sequence effects were observed for all cognitive outcomes in our linear mixed models. For the subset of participants with complete data in cycle 1, metformin was associated with better performance than placebo on tests of declarative and working memory. We present evidence that a clinical trial examining the effects of metformin on cognition and brain structure is feasible in long-term survivors of pediatric brain tumors and that metformin is safe to use and tolerable in this population. This pilot trial was not intended to test the efficacy of metformin for cognitive recovery and brain growth, but the preliminary results are encouraging and warrant further investigation in a large multicenter phase 3 trial.

Project description:BACKGROUND:Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested prior to training as a means to enhance the protein balance during exercise without spoiling the effect of the low carbohydrate availability. Accordingly, this is being practiced by world class athletes. However, the effect of protein intake on muscle protein metabolism during training low has not been studied. This study aimed to examine if protein intake prior to exercise with reduced carbohydrate stores benefits muscle protein metabolism in exercising and non-exercising muscles. METHODS:Nine well-trained subjects completed two trials in random order both of which included a high-intensity interval ergometer bike ride (day 1), a morning (day 2) steady state ride (90?min at 65% VO2peak, 90ss), and a 4-h recovery period. An experimental beverage was consumed before 90ss and contained either 0.5?g whey protein hydrolysate [WPH]/ kg lean body mass or flavored water [PLA]. A stable isotope infusion (L-[ring-13C6]-phenylalanine) combined with arterial-venous blood sampling, and plasma flow rate measurements were used to determine forearm protein turnover. Myofibrillar protein synthesis was determined from stable isotope incorporation into the vastus lateralis. RESULTS:Forearm protein net balance was not different from zero during 90ss exercise (nmol/100?ml/min, PLA: 0.5?±?2.6; WPH: 1.8, ± 3.3) but negative during the 4?h recovery (nmol/100?ml/min, PLA: -?9.7?±?4.6; WPH: -?8.7?±?6.5); no interaction (P?=?0.5) or main effect of beverage (P?=?0.11) was observed. Vastus lateralis myofibrillar protein synthesis rates were increased during 90ss exercise (+?0.02?±?0.02%/h) and recovery (+?0.02?±?0.02%/h); no interaction (P?=?0.3) or main effect of beverage (P?=?0.3) was observed. CONCLUSION:We conclude that protein ingestion prior to endurance exercise in the energy- and carbohydrate-restricted state does not increase myofibrillar protein synthesis or improve net protein balance in the exercising and non-exercising muscles, respectively, during and in the hours after exercise compared to ingestion of a non-caloric control. TRIAL REGISTRATION:clinicaltrials.gov, NCT01320449. Registered 10 May 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03147001.

Project description:PurposeTo determine the recovery kinetics of performance and exercise-induced muscle damage following different sprint-training protocols.MethodsIn a crossover design, ten male and female athletes (20.6 ± 2.4 years) performed 2 × (3 × 20 m: 2 min rest) and 1× (3 × 30 m: 3 min rest) of: (a) unresisted sprints (UST), (b) resisted sprints with 10% of body mass (BM) load (RST10), (c) resisted sprints with 20% BM load (RST20), against a control trial (no-training).ResultsBlood lactate (mmol/L) increased post-training versus pre-training in all sprint-training trials (6.7 ± 2.4 vs 1.2 ± 0.2, 5.6 ± 2.4 vs 1.3 ± 0.3, 7.3 ± 2.7 vs 1.2 ± 0.3, in UST, RST10, RST20, respectively), as did creatine kinase (U/L) 24 h, 48 h and 72 h post-training (UST: 251 ± 173, 238 ± 154, 209 ± 115 vs 155 ± 9, RST10: 252 ± 134, 240 ± 83, 218 ± 103 vs 164 ± 106; RST20: 237 ± 133, 323 ± 303, 262 ± 184 vs 179 ± 106, respectively). DOMS of knee-extensors (KE) and knee-flexors (KF) increased post-training up to 72 h in all sprint-training trials versus pre-training (ranging from 1.6 ± 1.3 to 3.8 ± 2.8 vs 1.0 ± 0, respectively). Eccentric torque (N m) of the KE of the non-dominant limb, decreased 24 h post-training versus pre-training in all sprint-training trials (UST: 249 ± 49 vs 266 ± 54; RST10: 229 ± 52 vs 273 ± 72; RST20: 253 ± 6 vs 262 ± 56), as did that of the KF of the dominant limb (UST: 135 ± 29 vs 144 ± 26; RST10: 130 ± 29 vs 140 ± 25; RST20: 139 ± 33 vs 142 ± 26). 10-m sprint-time (s) increased 48 h post-training versus pre-training (1.81 ± 0.15 vs 1.77 ± 0.11), and 30-m sprint-time increased 24 h, 48 h, 72 h post-training versus pre-training (4.35 ± 0.36, 4.40 ± 0.44, 4.33 ± 0.41 vs 4.21 ± 0.34, respectively), only in RST20.ConclusionsUnresisted and resisted sprint-training induces prolonged reduction of muscle strength (24 h), and sprinting performance (72 h), associated with prolonged increase of DOMS and CK (72 h).

Project description:BackgroundMany breast cancer survivors (BCS) report deficits in cognitive function. Physical activity (PA) has been associated with better processing speed and memory in healthy adults and thus may be a useful method for improving cognition in BCS. The purpose of this study was to examine the effects of an acute bout of PA on processing speed and spatial working memory in a sample of BCS.MethodsUsing a repeated measures, crossover design, BCS [N = 27; Mage (SD) = 49.11(8.05)] completed two sessions in counterbalanced order: 30 min of moderate-intensity treadmill walking and 30 min of seated rest. Women completed cognitive tasks immediately before and after each session.ResultsWithin-subjects repeated measures analyses of variance revealed a significant time by session effect for processing speed reaction time [F (1,25) = 5.02, p = .03, η2 = 0.17]. This interaction was driven by significantly reduced reaction time (e.g., faster response) post-exercise and no change post-rest. Further between-subjects analyses indicated a significant time by session by moderate to vigorous physical activity (MVPA) split [F (1,25) = 5.23, p = .03, η2 = 0.17], such that women who engaged in ≥45 min of average daily MVPA reduced their reaction time post-exercise (p = .01) and increased RT post-rest (p = .06). Time by session effects for spatial working memory 3-item accuracy and 4-item reaction time trended towards significance, p = 0.08 and p = 0.10, respectively, again driven by better performance post-exercise.ConclusionsThe moderate effect of acute exercise on domains of memory and processing speed in BCS is encouraging. Cancer-related cognitive impairment remains largely misunderstood; however, the results from the present study offer preliminary evidence for the positive relationship between acute exercise and cognition in BCS.Trial registrationClinicalTrials.gov NCT02592070 . Registered 30 October 2015. Retroactively registered.

Dataset Information

Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training.

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Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training.

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