Clinical trial NCT02083445: Exercise, Hypoxia and CPC in TBI Patients
Official title: Exercise, Muscle Electro-stimulation and Intermittent Hypobaric Hypoxia Program and Circulating Progenitor Cells in Traumatic Brain Injured Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Traumatic Brain Injury
Keywords: Traumatic brain injury
Exercise
Psychology
Physiology
Progenitor cells
Hypoxia
Lead sponsor: University of Barcelona
Sponsor class: OTHER
Collaborators: name: Ministerio de Economía y Competitividad, Spain
First posted: 2014-03-11
Enrollment: 21
Sex: MALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from initial physical stress test at one week post-intervention
timeFrame: One week before and an expected average of one week after the intervention
measure: Change from initial psychological test at one weeks after intervention
timeFrame: One week before and an average of one week after the intervention
Secondary outcomes:
measure: Circulating progenitor cells increase
timeFrame: The day before, every 15 days during the intervention and two weeks after the intervention
Other outcomes:
measure: Relationship between circulating progenitor cells and physical or psychological tests improvement
timeFrame: An average of two weeks after intervention
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: University of Barcelona
state: Barcelona
Study officials:
affiliation: University of Barcelona and Bellvitge University Hospital
name: Luisa Corral, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universiy of Barcelona
name: Casimiro F Javierre, MD, PhD
role: STUDY_DIRECTOR
affiliation: University of Barcelona
name: Ginés Viscor, PhD
role: STUDY_CHAIR
affiliation: Bellvitge University Hospital
name: Josep L Ventura, MD, PhD
role: STUDY_DIRECTOR
References:
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