Exercise, Hypoxia and CPC in TBI Patients

Traumatic Brain Injury Clinical Trial

— TCECAM  

Official title:

Exercise, Muscle Electro-stimulation and Intermittent Hypobaric Hypoxia Program and Circulating Progenitor Cells in Traumatic Brain Injured Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02083445
• Other study ID #: DEP2010-222005-C02-02
• Secondary ID: AC048-10, PR017/
• Status: Completed
• Phase: N/A
• First received: March 1, 2014
• Last updated: March 7, 2014
• Start date: November 2011
• Est. completion date: February 2014

Study information

• Verified date: March 2014
• Source: University of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial Summary

Circulating progenitor cells (CPC) treatments may have great potential for the recovery of neurons and brain function. Our group has reported how exposure to intermittent hypobaric hypoxia with superficial muscle electrostimulation is able to increase the concentration of CPC in peripheral blood in humans. Therefore, we believe that through physical activities and exposure to intermittent hypobaric hypoxia for a period, it will increase CPC in the blood of subjects who have suffered a severe Traumatic Brain Injury (TBI) one or more years ago, promoting regeneration and functional and cognitive recovery. The study primary end-point is to improve physical or psychological functioning of participants with TBI with a program of exercise, muscle electro-stimulation (ME) and/or intermittent-hypobaric-hypoxia (IHH). Secondary end-points are to increase and maintain CPC and also to study their possible relationship with physical or psychological improvement of participants with Traumatic Brain Injury (TBI). In order to achieve these objectives investigators have designed a randomized controlled trial that will include those patients who suffered severe TBI more than one year previously with physical or psychological sequelae. Exercise, muscle electro-stimulation (ME) and/or intermittent hypobaric hypoxia (IHH) programs will be applied during twelve weeks. Psychological and physical stress tests will carry out before and after the program and CPC will measure at the beginning, every two weeks, and at the end of the program.

Description:

Clinical, experimental, case control and prospective study. Inclusion criteria are: patients who suffered severe TBI more than one year previously with physical or psychological sequelae, male sex, and age 20-60 years old. Patients with epilepsy are not included. The study was approved by the institution's Research Ethics Committee and informed consent was obtained from the patients.

A program of three days per week during twelve weeks will be applied to the active groups:

one, exercise and muscle electrical stimulation, and the other, exercise, muscle electrical stimulation and IHH chamber exposure. Control group participants will follow a a day of cognitive activities one day per week during 12 weeks.

Psychological and physical stress tests are carried out before and after the program. Psychological tests evaluate features of language and work (verbal memory-RAVLT), Trail Making Test (TMT A and B), Stroop Test, working memory capacity and attention (WAIS III), information processing speed (WAIS III), orientation and verbal fluency (Barcelona test), executive functions (WAIS III and Tower of London tests) and estimated premorbid intelligence index (vocabulary, WAIS III). Reduced Paced Auditory Serial Addition Test (PASAT-G) evaluate work memory components. Physical graded maximum stress tests were performed on a cycle ergometer increasing progressively the workload, in order to evaluate physical capacity and adaptation to different intensities of effort. CPC (CD34+) are measured in peripheral blood according to a previously used method (Viscor et al., 2009), at the beginning, every two weeks, and at the end of the program (blood samples were always obtained before the exercise sessions).

Statistical analysis: data will express as mean, median, standard deviation and interquartile range as appropriate. The continuous variables will compare using the Mann-Whitney U test. Wilcoxon signed rank test and Friedman test are used for repeated measures. All tests will perform using Statistical Package for the Social Sciences (SPSS) v.13. Statistical significance was set at P<0.05.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 20 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients who suffered severe TBI more than one year previously with physical or psychological sequelae.

• Written informed consent from patient

Exclusion Criteria:

• Epilepsy

• Any medical or psychological contraindications for implementing the program of physical activity or hypobaric chamber.

• Inclusion in other ongoing study

• Refuse consent

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Brain Injuries
• Traumatic Brain Injury

Intervention

Other:
• cognitive activities
Participants followed a day of cognitive activities 1 day (1 hour/day) per week during 12 weeks.
• Exercise program
Exercise program of endurance, resistance and proprioception exercises, comprising three sessions per week and muscle electro-stimulation was applied using the Compex Vitality® vascular and capillarization program with electrodes fixed in quadriceps and abdominal muscles or cycling exercise.

Device:
• Muscle electro-stimulation
A program of intermittent hypobaric hypoxia and muscle electro-stimulation of 3 days (3 hours/day) per week during 12 weeks

Other:
• Intermittent hypobaric hypoxia

Locations

Country	Name	City	State
Spain	University of Barcelona	L'Hospitalet de Llobregat	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
University of Barcelona	Ministry of Economy and Competitiveness, Spain

Country where clinical trial is conducted

Spain, 

References & Publications (13)

Bennie SD, Petrofsky JS, Nisperos J, Tsurudome M, Laymon M. Toward the optimal waveform for electrical stimulation of human muscle. Eur J Appl Physiol. 2002 Nov;88(1-2):13-9. Epub 2002 Sep 10. — View Citation

Bonsignore MR, Morici G, Riccioni R, Huertas A, Petrucci E, Veca M, Mariani G, Bonanno A, Chimenti L, Gioia M, Palange P, Testa U. Hemopoietic and angiogenetic progenitors in healthy athletes: different responses to endurance and maximal exercise. J Appl Physiol (1985). 2010 Jul;109(1):60-7. doi: 10.1152/japplphysiol.01344.2009. Epub 2010 May 6. — View Citation

Corral L, Javierre CF, Ventura JL, Marcos P, Herrero JI, Mañez R. Impact of non-neurological complications in severe traumatic brain injury outcome. Crit Care. 2012 Dec 12;16(2):R44. doi: 10.1186/cc11243. — View Citation

Corral L, Ventura JL, Herrero JI, Monfort JL, Juncadella M, Gabarrós A, Bartolomé C, Javierre CF, García-Huete L. Improvement in GOS and GOSE scores 6 and 12 months after severe traumatic brain injury. Brain Inj. 2007 Nov;21(12):1225-31. doi: 10.1080/02699050701727460. — View Citation

Driver S, Ede A. Impact of physical activity on mood after TBI. Brain Inj. 2009 Mar;23(3):203-12. doi: 10.1080/02699050802695574. — View Citation

Guo X, Liu L, Zhang M, Bergeron A, Cui Z, Dong JF, Zhang J. Correlation of CD34+ cells with tissue angiogenesis after traumatic brain injury in a rat model. J Neurotrauma. 2009 Aug;26(8):1337-44. doi: 10.1089/neu.2008-0733. — View Citation

Koutroumpi M, Dimopoulos S, Psarra K, Kyprianou T, Nanas S. Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects. World J Cardiol. 2012 Dec 26;4(12):312-26. doi: 10.4330/wjc.v4.i12.312. — View Citation

Möbius-Winkler S, Hilberg T, Menzel K, Golla E, Burman A, Schuler G, Adams V. Time-dependent mobilization of circulating progenitor cells during strenuous exercise in healthy individuals. J Appl Physiol (1985). 2009 Dec;107(6):1943-50. doi: 10.1152/japplphysiol.00532.2009. Epub 2009 Oct 1. — View Citation

Ploughman M. Exercise is brain food: the effects of physical activity on cognitive function. Dev Neurorehabil. 2008 Jul;11(3):236-40. doi: 10.1080/17518420801997007. Review. — View Citation

Viscor G, Javierre C, Pagès T, Ventura JL, Ricart A, Martin-Henao G, Azqueta C, Segura R. Combined intermittent hypoxia and surface muscle electrostimulation as a method to increase peripheral blood progenitor cell concentration. J Transl Med. 2009 Oct 29;7:91. doi: 10.1186/1479-5876-7-91. — View Citation

Wang JS, Lee MY, Lien HY, Weng TP. Hypoxic exercise training improves cardiac/muscular hemodynamics and is associated with modulated circulating progenitor cells in sedentary men. Int J Cardiol. 2014 Jan 1;170(3):315-23. doi: 10.1016/j.ijcard.2013.11.005. Epub 2013 Nov 12. — View Citation

Xu Q, Wang S, Jiang X, Zhao Y, Gao M, Zhang Y, Wang X, Tano K, Kanehara M, Zhang W, Ishida T. Hypoxia-induced astrocytes promote the migration of neural progenitor cells via vascular endothelial factor, stem cell factor, stromal-derived factor-1alpha and monocyte chemoattractant protein-1 upregulation in vitro. Clin Exp Pharmacol Physiol. 2007 Jul;34(7):624-31. — View Citation

Zhu LL, Zhao T, Li HS, Zhao H, Wu LY, Ding AS, Fan WH, Fan M. Neurogenesis in the adult rat brain after intermittent hypoxia. Brain Res. 2005 Sep 7;1055(1-2):1-6. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Relationship between circulating progenitor cells and physical or psychological tests improvement	If a statistically significant increase of circulating progenitor cells occurs and physical and/or psychological tests improvement, their relationship will be analyzed	An average of two weeks after intervention	No
Primary	Change from initial physical stress test at one week post-intervention	Physical graded maximum stress tests are performed on a cycle ergometer controlling the workload, in order to evaluate physical capacity and adaptation to different intensities of effort.While performance of these tests are conducted, cardiocirculatory (control of heart rate, blood pressure measurement, continuous ECG) and respiratory (breathing gases analysis) are monitored to observe the adaptation to the effort.	One week before and an expected average of one week after the intervention	Yes
Primary	Change from initial psychological test at one weeks after intervention	Psychological tests evaluated features of language and work (verbal memory-RAVLT), Trail Making Test (TMT A and B), Stroop Test, working memory capacity and attention (WAIS III), information processing speed (WAIS III), orientation and verbal fluency (Barcelona test), executive functions (WAIS III and Tower of London tests) and estimated premorbid intelligence index (vocabulary, WAIS III). Reduced Paced Auditory Serial Addition Test (PASAT-G)	One week before and an average of one week after the intervention	Yes
Secondary	Circulating progenitor cells increase	Blood CD34 staining and flow cytometry assay in accordance with ISHAGE guidelines (Keeney et al., 1998). CD34 cells/µL.	The day before, every 15 days during the intervention and two weeks after the intervention	No