Exercise, Hypoxia and CPC in TBI Patients

NCT02083445 | Completed DMC

• 2 other identifiers: DEP2010-222005-C02-02AC048-10, PR017/10
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Traumatic Brain Injury

Keywords

Traumatic brain injury; Exercise; Psychology; Physiology; Progenitor cells; Hypoxia

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (1)

• Circulating progenitor cells increase

  The day before, every 15 days during the intervention and two weeks after the intervention

Other Outcomes (1)

• Relationship between circulating progenitor cells and physical or psychological tests improvement

  An average of two weeks after intervention

Study Arms (3)

Control group

PLACEBO COMPARATOR

Once a week there will be an attendance cognitive session (specific sessions designed to work on aspects related to body perception, movement, space) and the extraction of blood samples will be carried out to determine the progenitor cells on the same day of the active groups.

Other: cognitive activities

Exercise group

ACTIVE COMPARATOR

Patients with past history of TBI will perform exercise sessions two hours three days a week during 12 weeks. The sessions will consist of aerobic, strength, flexibility, proprioception and balance activities and muscle electro-stimulation sessions or cycling sessions.

Other: Exercise program

Muscle electro-stimulation and IHH

ACTIVE COMPARATOR

Patients with past history of TBI will perform a 12 weeks program: intermittent hypobaric hypoxia (IHH) 2 hours at a simulated altitude of 4500 meters 3 days/week. Muscle electro-stimulation for two periods of 20 minutes during the stay in the hypobaric chamber.

Device: Muscle electro-stimulation; Other: Intermittent hypobaric hypoxia

Interventions

cognitive activities OTHER

Participants followed a day of cognitive activities 1 day (1 hour/day) per week during 12 weeks.

Control group

Exercise program OTHER

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.

Exercise group

Muscle electro-stimulation DEVICE

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

Muscle electro-stimulation and IHH

Intermittent hypobaric hypoxia OTHER

Muscle electro-stimulation and IHH

Eligibility Criteria

• Age: 20 Years - 60 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who suffered severe TBI more than one year previously with physical or psychological sequelae.
• Written informed consent from patient

You may not qualify if:

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

Sponsors & Collaborators

• University of Barcelona: lead
• Ministerio de Economía y Competitividad, Spain: collaborator

Study Sites (1)

University of Barcelona

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Related Publications (13)

• Viscor G, Javierre C, Pages 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.

  PMID: 19874615 BACKGROUND

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

  PMID: 22410278 BACKGROUND

• Corral L, Ventura JL, Herrero JI, Monfort JL, Juncadella M, Gabarros A, Bartolome C, Javierre CF, Garcia-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.

  PMID: 18236198 BACKGROUND

• 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. doi: 10.1007/s00421-002-0711-4. Epub 2002 Sep 10.

  PMID: 12436266 BACKGROUND

• 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.

  PMID: 20448032 BACKGROUND

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

  PMID: 19205956 BACKGROUND

• 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.

  PMID: 19226208 BACKGROUND

• 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.

  PMID: 23272272 BACKGROUND

• 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.

  PMID: 18781504 BACKGROUND

• Mobius-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.

  PMID: 19797690 BACKGROUND

• 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.

  PMID: 24286591 BACKGROUND

• 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. doi: 10.1111/j.1440-1681.2007.04619.x.

  PMID: 17581219 BACKGROUND

• 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. doi: 10.1016/j.brainres.2005.04.075.

  PMID: 16098951 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic; Motor Activity; Hypoxia

Interventions

Resistance Training

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Behavior; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Luisa Corral, MD, PhD

  University of Barcelona and Bellvitge University Hospital

  PRINCIPAL INVESTIGATOR

• Casimiro F Javierre, MD, PhD

  Universiy of Barcelona

  STUDY DIRECTOR

• Ginés Viscor, PhD

  University of Barcelona

  STUDY CHAIR

• Josep L Ventura, MD, PhD

  Bellvitge University Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Luisa Corral

Study Record Dates

• First Submitted: March 1, 2014
• First Posted: March 11, 2014
• Study Start: November 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: February 1, 2014
• Last Updated: March 11, 2014

Record last verified: 2014-03

Locations

ES (1)