NCT02441179

Brief Summary

Spinal cord injury (SCI) interrupts descending synaptic pathways from brainstem premotor neurons to spinal motor neurons, thereby paralyzing muscles below the neurological level. In recent years, considerable evidence has demonstrated that acute intermittent hypoxia (AIH) elicits plasticity in the spinal cord and strengthens spare synaptic pathways which is expressed as respiratory and somatic functional recovery in animals and humans suffering from incomplete SCI. The fundamental hypothesis guiding this project is that AIH-induced motor plasticity can be "harnessed" to improve walking capacity in incomplete SCI patients, classified as C and D categories according to International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). The inclusion criteria include patients \> 18 years-old, with traumatic or non-traumatic, non-progressive incomplete SCI, onset \> 6 months, neurological level C5-T12, with walking ability with or without assistive devices, without joint contractures, orthopedic injuries, osteoporosis, cutaneous lesions, cardiopulmonary complications and a body weight below 150 Kg. A randomized, triple-blind, placebo-controlled parallel design study will be done including 100% of patients fulfilling the criteria. Participants will receive repetitive acute intermittent hypoxia (rAIH: 15 episodes of 90 second 9% inspired oxygen interspersed with 90-second normoxia) or repetitive continued normoxia (rSham: 21% inspired oxygen) combined with 45 minutes body weight-supported treadmill training on 5 consecutive days and then three times per week for 3 weeks. Primary outcome measurement will be the 10-meter walking test. Secondary outcome measurements include the 6-minute walking test, timed up and go test, body/weight load, modified ashworth scale and visual analog scale. All outcomes will be measured before beginning the protocol (baseline), after five days of AIH/Sham (D5), weekly up to the end of the study (W2-W4), and a post-study follow-up for 2 weeks (F1-F2). Aditionally, cognitive assesment before and after the study will be performed using the "Figura compleja de Rey-Osterrieth" and the "Test de aprendizaje verbal España Complutense (TAVEC)". Repetitive AIH and body weight-supported treadmill training may represent a novel, safe, and noninvasive potential therapy to partially restore walking function in incomplete sub-acute and chronic SCI patients, a population with limited, if any, potential for improved function.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
35

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Mar 2015

Shorter than P25 for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2015

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

May 5, 2015

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 12, 2015

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
8 months until next milestone

Results Posted

Study results publicly available

May 27, 2016

Completed
Last Updated

May 27, 2016

Status Verified

January 1, 2016

Enrollment Period

7 months

First QC Date

May 5, 2015

Results QC Date

October 28, 2015

Last Update Submit

April 21, 2016

Conditions

Spinal Cord Injuries

Keywords

acute intermittent hypoxiarehabilitationspinal cord injury

Outcome Measures

Primary Outcomes (1)

  • Gait Speed With 10-Meter Walk Test

    The 10-meter walk test measures the time (in seconds) that it takes a patient to walk 10m.

    Change from baseline in gait speed five days after daily IH.

Secondary Outcomes (6)

  • Gait Endurance With the 6-Minute Walk Test

    Change from baseline in gait indurance five days after daily IH.

  • Gait Speed With the Timed up and go Test

    Change from baseline in gait speed five days after daily IH.

  • Percentage of Subjects With Worsening Muscle Tone on the Ashworth Scale

    Muscle tone at week 4.

  • Percentage of Subjects With Worsening Pain Perception on the "The Visual Analog Test"

    Pain perception at week 4

  • Learning and Memory With the Rey-Osterrieth Complex Figure (ROCF) Test

    Episodic visual memory at week 4.

  • +1 more secondary outcomes

Study Arms (2)

Acute Intermittent Hypoxia Arm

EXPERIMENTAL

AIH protocol: it consists of 15, 90-second hypoxic episodes (FiO2=0.09) interspersed with 15, 90-second normoxic intervals (FiO2=0.21) for a total time of 45 minutes. This protocol will be repeated every day for 5 consecutive days and then 3 times per week for 3 weeks. Total time: 4 weeks. After this AIH protocol, patients will received body weight-assisted treadmill training (BWSTT) for 45 minutes.

Other: Acute Intermittent HypoxiaOther: Body weight-assisted treadmill training

Normoxia Arm

PLACEBO COMPARATOR

Sham protocol: it consists of continuous normoxia (FiO2=0.21) for 45 minutes for 5 consecutive days and then 3 times per week for 3 weeks. Total time: 4 weeks.After this AIH protocol, patients will received body weight-assisted treadmill training (BWSTT) for 45 minutes.

Other: Body weight-assisted treadmill trainingOther: Sham Protocol

Interventions

Acute Intermittent HypoxiaOTHER

Patients will breath 9% oxigen for 1.5 minutes interspersed with 1.5 minutes of 21% oxigen (normoxia), 15 times for a total of 45 minutes.

Acute Intermittent Hypoxia Arm
Body weight-assisted treadmill trainingOTHER

Patient´s gait will be trained through a weight-assisted treadmill (BWSTT). All recruited patients will start BWSTT at a speed of 0.6 km/hr. The physical therapist will manually correct posture to assure an adequate gait, increasing the speed of treadmill progressively depending upon the patient progress and tolerance. This training will be done immediately after the protocol of AIH or Sham and it will last 45 minutes.

Acute Intermittent Hypoxia ArmNormoxia Arm
Sham ProtocolOTHER

It consists of continuous normoxia (FiO2=0.21) for 45 minutes for 5 consecutive days and then 3 times per week for 3 weeks. Total time: 4 weeks.

Also known as: Placebo Protocol
Normoxia Arm

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients ≥ 18 years-old from "Instituto Teletón Santiago" and "Hospital Clínico Mutual de seguridad".
  • C5 to T12 spinal cord injury, classified as ISNCSCI grades C and D
  • Traumatic and non-traumatic, non-progressive lesions
  • Onset \> 6 months
  • Ability to ambulate with or without assistive devices
  • Ability to follow verbal or visual commands
  • Signed informed consent

You may not qualify if:

  • Orthopedic injuries that are unstable
  • Osteoporosis with high risk of pathological fracture
  • Cutaneous lesions and/or pressure ulcers
  • Joint contractures
  • Cardiopulmonary diseases
  • Body weight exceeding 150 Kg

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Instituto de Rehabilitación Infantil Teletón

Santiago, Santiago Metropolitan, 8320000., Chile

Location

Hospital Mutual de Seguridad

Santiago, Santiago Metropolitan, 9160000, Chile

Location

Related Publications (1)

  • Navarrete-Opazo A, Alcayaga JJ, Sepulveda O, Varas G. Intermittent Hypoxia and Locomotor Training Enhances Dynamic but Not Standing Balance in Patients With Incomplete Spinal Cord Injury. Arch Phys Med Rehabil. 2017 Mar;98(3):415-424. doi: 10.1016/j.apmr.2016.09.114. Epub 2016 Oct 1.

    PMID: 27702556DERIVED

MeSH Terms

Conditions

Spinal Cord Injuries

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesTrauma, Nervous SystemWounds and Injuries

Limitations and Caveats

Our study included only 4 female subjects; thus, we could not investigate gender differences in response to IH.

Results Point of Contact

Title
Dr. Angela Navarrete-Opazo
Organization
Teleton Institute
angelaandrean@gmail.com
+56 0226772075

Study Officials

  • Angela A Navarrete-Opazo, MD, PhD

    Instituto de Rehabilitación Infantil Teletón

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Angela A Navarrete-Opazo MD, PhD

Study Record Dates

First Submitted

May 5, 2015

First Posted

May 12, 2015

Study Start

March 1, 2015

Primary Completion

October 1, 2015

Study Completion

October 1, 2015

Last Updated

May 27, 2016

Results First Posted

May 27, 2016

Record last verified: 2016-01

Locations

CL(2)