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Spinal Cord InjuryNCT01538693

Molecular Markers of Neuroplasticity During Exercise in People With Incomplete Spinal Cord Injury

A study testing escitalopram oxalate, Cyproheptadine and sugar pill in people with Spinal Cord Injury, run by T. George Hornby at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine whether exercising (walking) at different intensities increases levels of factors in the blood and saliva that are known to impact neuroplasticity (how the connections in the spinal cord and brain can change) and if these levels are changed by pairing exercise with a single… Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Spinal Cord Injury
What is being tested?
escitalopram oxalate, Cyproheptadine and sugar pill
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteUnited States
Study dates
Dec 2011to May 2015
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Must be motor incomplete spinal cord injury (ASIA C or D) of 1 year or greater duration, with anatomical lesions between C1-T10
  • Must be between 18 and 75 years of age
  • Must be ambulatory with passive range of motion consistent with normal walking, and must include: ankle dorsiflexion ankle to 10° and plantarflexion to 30°, knee flexion from 0 to 90°, hip flexion/extension to 90° to -10°.
  • Must be medically stable with medical clearance to participate, with absence of concurrent severe medical illness including: unhealed decubiti, existing infection, significant cardiovascular or metabolic disease which limits exercise participation, significant osteoporosis (as indicated by history of fractures following injury), active heterotrophic ossification in the lower extremities, known history of peripheral nerve injury in lower legs, history of known traumatic head injury, mental illness, history of pre-existing QT interval prolongation, congenital long QT syndrome, and history of pulmonary complications, including significant obstructive and/or restrictive lung diseases
  • May be undergoing concurrent physical therapy
  • May be of childbearing potential (for women)
  • Men and women will be recruited for participation in the proposed study at rates consistent with national and local average of gender disparities of SCI (80% male, 20% women)
  • Individuals of different ethnicities will be recruited at rates similar to the national and local ethnicity rates. Current data since 2005 indicate that of the entire population of SCI, 66.1% are Caucasian, 27.1% are African American, 6.6% are of Hispanic origin, and 2.0% are Asian.

Who cannot join

  • Weighing more than 300lbs
  • Ventilator-dependency
  • Use of substantial orthopedic bracing to stabilize the cervical or thoracic vertebral column
  • Inability to tolerate 10 minutes of standing without orthostasis (decrease in blood pressure by 20 mmHg systolic and 10 mmHg diastolic).
  • Women who are pregnant or who are considering becoming pregnant will be excluded due to the trunk and pelvis restraints required for use during locomotion, and secondary to the unknown effects of the pharmacological agents on the developing fetus
  • Exhibiting symptoms suggestive of depression according to the Personal health Questionaire (PHQ-9)
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  • Subjects who exhibit hemoglobin levels consistent with anemia (<13g/dL for men and <12g/dL for women) will be excluded from the study.
  • Currently taking prescribed anti-depressant medications, including specific monoaminergic agents, their precursors or their agonists, antipsychotics, medications known to prolong the QT interval, or other medications with known interactions to the SSRIs. All subjects will be excluded from participation unless both attending physician and patient agree to cease all such medications during the evaluation and training period. A 14-day washout period for SSRIs and a 72 hour washout for Tizanidine will be utilized. Subjects will be financially responsible for the physician visits necessary to wean from medication. Completion of appropriate and safe weaning will be confirmed by the patients' physician.
  • Currently taking prescribed anti-spastic medications. Specific agents to be excluded include baclofen (Lioresal®) and benzodiazepines (Diazepam®). Selected agents used for pain modulation will be evaluated per subject to ascertain potential interactions with test agent. All subjects will be excluded from participation unless both attending physician and patient agree to cease all such medications during the evaluation and training period. A 72-hour minimum washout period for all such medications will be utilized. Subjects will be financially responsible for the physician visits necessary to wean from medication. Completion of appropriate and safe weaning will be confirmed by the patients' physician.
  • Clinically diagnosed liver, renal, or other metabolic disease that may interfere with drug action and/or clearance

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Rehabiliation Institute of Chicago

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: Molecular Markers of Neuroplasticity During High-Intensity Exercise in Subjects With Incomplete Spinal Cord Injury

The purpose of this study is to determine whether exercising (walking) at different intensities increases levels of factors in the blood and saliva that are known to impact neuroplasticity (how the connections in the spinal cord and brain can change) and if these levels are changed by pairing exercise with a single dose of commonly used prescription drugs or by your mood.

Read the detailed description

The protein brain-derived neurotrophic factor (BDNF) is known to promote cell survival, improve synaptic function, and induce neuronal morphological changes. Consequently, BDNF plays a major role in neuroplasticity and the ability of the central nervous system to adapt and recover following injury. Regardless of the molecular mechanisms by which this occurs (which are poorly understood), potentiating the expression of BDNF following spinal cord injury has been shown to improve functional outcomes in animals.(1, 2) It is well documented in both animal and human literature that the production BDNF increases with physical exercise in healthy populations and individuals with chronic disease or disability. (3) The literature suggests that this increase is proportional to the intensity of exercise, though the parameters of exercise to maximize this effect are poorly understood. (2, 4-6) From animal research, it has been postulated that serotonin (5HT) plays a role in the mechanism of increase in BDNF expression, (7-9) with findings that specifically demonstrate potentiation of the exercise-induced expression with antidepressant treatment(10)and a blunted response when monoaminergic signaling is blocked.(11) A specific genetic variation in the BDNF gene, found in approximately 30% of the population has also been noted as an important factor in the proper release of BDNF with associated deficits in motor learning. (12, 13) Initial evidence also suggests that this polymorphism may have an impact of the relationship between exercise and BDNF. (14, 15) The objective of this study is the evaluate the response of serum concentrations of brain-derived neurotrophic factor ([BDNF]s) to an acute bout of exercise in ambulatory people with incomplete spinal cord injury; additionally, to examine the effect of pharmacological agents that alter serotonergic (5HT) transmission on this exercise-induced change in [BDNF]s. To achieve this objective we will investigate [BDNF]s during a treadmill test alone and in combination with two commonly used medications; escitalopram oxalate , a selective-5HT reuptake inhibitor (SSRI) and cyproheptadine (CYPRO), a 5HT antagonist.

Studies have also shown a relationship of BDNF to mood, in particular, depression. A secondary study will be performed in parallel with the primary study with the purpose of examining mood and how it correlates with the molecular markers for neuroplasticity as individuals participate in the repeated exercise and the other stated interventions. As the subjects progress over the course of the study time mood may change and may impact the relationship of the BDNF to the primary interventions.

Being tested
escitalopram oxalate, Cyproheptadine, sugar pill, Graded intensity exercise
Keywords
BDNF, serotonin, high-intensity, exercise
Medical subject headings
Spinal Cord Injuries, Motor Activity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • escitalopram oxalateDrug

    Also called Lexapro

    10 mg 4.5 hours prior to testing

  • CyproheptadineDrug

    8mg 4.5 hours prior to testing

  • sugar pillDrug

    4.5 hour prior to testing

  • Graded intensity exerciseOther

    modified bruce protocol for peak oxygen consumption testing

Study groups in NCT01538693
Study groupRoleWhat they receive
escitalopram oxalateActive comparatorExercise testing with escitalopram oxalate dose
Receives: Drug: escitalopram oxalate; Other: Graded intensity exercise
cyproheptadineActive comparatorexercise testing with cyproheptadine dose
Receives: Drug: Cyproheptadine; Other: Graded intensity exercise
placeboPlacebo comparatorexercise testing with placebo dose
Receives: Drug: sugar pill; Other: Graded intensity exercise

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in blood serum concentration of neuroplastic proteins

    During a graded treadmill test, 5mL of blood will be taken at each speed the subject is able to obtain before failure. 5mL of blood will also be taken immediately after completion of the treadmill test and every 10 minutes for up to 30 minutes after completion.

    Measured: assessed prior to, throughout, and following the duration of a graded exercise test, over an expected average of 2 hours

Secondary outcomes (11)
  1. fastest possible walking velocity overground

    Measured: one time, baseline measure

  2. Six Minute Walk Distance

    Measured: one time basline measurement

  3. Volitional strength: Lower Extremity Motor Score

    Measured: one time baseline measure

  4. Modified Ashworth Scale

    Measured: one time baseline measurement

  5. Spinal Cord Assessment tool for Spasticity

    Measured: one time baseline measure

  6. Measure of Community mobility

    Measured: Step activity monitor worn on lower extremity for 7 days

  7. Sagittal plane kinematics of excursions of hip/knee/ankle

    Measured: continuous assessment for an average of ten minutes at each visit

  8. Peak ambulation velocity

    Measured: One time measure at the end of each graded intensity treadmilll test

  9. Oxygen consumption

    Measured: continuous assessment for an average of ten minutes at each visit

  10. Heart Rate

    Measured: continuous assessment for an average of ten minutes at each visit

  11. Rating of Perceived Exertion (Borg Scale)

    Measured: continuous assessment for an average of ten minutes at each visit

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2012 (estimated)
  2. Study startDec 2011
  3. Primary completionMay 2015
  4. Study completionMay 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01538693
Sponsor's protocol ID
STU00056144
Status last verified
May 2015
First submitted
24 Jan 2012
Last updated
19 May 2015
Results posted
No
Data monitoring committee
No

Publications

  • Ying Z, Roy RR, Zhong H, Zdunowski S, Edgerton VR, Gomez-Pinilla F. BDNF-exercise interactions in the recovery of symmetrical stepping after a cervical hemisection in rats. Neuroscience. 2008 Sep 9;155(4):1070-8. doi: 10.1016/j.neuroscience.2008.06.057. Epub 2008 Jul 3.

    PubMed 18672032
  • Ying Z, Roy RR, Edgerton VR, Gomez-Pinilla F. Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury. Exp Neurol. 2005 Jun;193(2):411-9. doi: 10.1016/j.expneurol.2005.01.015.

    PubMed 15869943
  • Knaepen K, Goekint M, Heyman EM, Meeusen R. Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects. Sports Med. 2010 Sep 1;40(9):765-801. doi: 10.2165/11534530-000000000-00000.

    PubMed 20726622
  • Ferris LT, Williams JS, Shen CL. The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function. Med Sci Sports Exerc. 2007 Apr;39(4):728-34. doi: 10.1249/mss.0b013e31802f04c7.

    PubMed 17414812
  • Cotman CW, Berchtold NC. Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci. 2002 Jun;25(6):295-301. doi: 10.1016/s0166-2236(02)02143-4.

    PubMed 12086747
  • Neeper SA, Gomez-Pinilla F, Choi J, Cotman CW. Physical activity increases mRNA for brain-derived neurotrophic factor and nerve growth factor in rat brain. Brain Res. 1996 Jul 8;726(1-2):49-56.

    PubMed 8836544
  • Ivy AS, Rodriguez FG, Garcia C, Chen MJ, Russo-Neustadt AA. Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant. Pharmacol Biochem Behav. 2003 Apr;75(1):81-8. doi: 10.1016/s0091-3057(03)00044-3.

    PubMed 12759116
  • Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci. 1995 Nov;15(11):7539-47. doi: 10.1523/JNEUROSCI.15-11-07539.1995.

    PubMed 7472505
  • Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW. Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience. 2000;101(2):305-12. doi: 10.1016/s0306-4522(00)00349-3.

    PubMed 11074154
  • Russo-Neustadt A, Beard RC, Cotman CW. Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology. 1999 Nov;21(5):679-82. doi: 10.1016/S0893-133X(99)00059-7.

    PubMed 10516964
  • Garcia C, Chen MJ, Garza AA, Cotman CW, Russo-Neustadt A. The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal brain-derived neurotrophic factor transcripts following voluntary physical activity. Neuroscience. 2003;119(3):721-32. doi: 10.1016/s0306-4522(03)00192-1.

    PubMed 12809693
  • Pearson-Fuhrhop KM, Cramer SC. Genetic influences on neural plasticity. PM R. 2010 Dec;2(12 Suppl 2):S227-40. doi: 10.1016/j.pmrj.2010.09.011.

    PubMed 21172685
  • Cheeran B, Talelli P, Mori F, Koch G, Suppa A, Edwards M, Houlden H, Bhatia K, Greenwood R, Rothwell JC. A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J Physiol. 2008 Dec 1;586(23):5717-25. doi: 10.1113/jphysiol.2008.159905. Epub 2008 Oct 9.

    PubMed 18845611
  • Bryan A, Hutchison KE, Seals DR, Allen DL. A transdisciplinary model integrating genetic, physiological, and psychological correlates of voluntary exercise. Health Psychol. 2007 Jan;26(1):30-9. doi: 10.1037/0278-6133.26.1.30.

    PubMed 17209695
  • Mata J, Thompson RJ, Gotlib IH. BDNF genotype moderates the relation between physical activity and depressive symptoms. Health Psychol. 2010 Mar;29(2):130-3. doi: 10.1037/a0017261.

    PubMed 20230085

Questions about this trial

What is this clinical trial studying?

A study testing escitalopram oxalate, Cyproheptadine and sugar pill in people with Spinal Cord Injury, run by T. George Hornby at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in blood serum concentration of neuroplastic proteins (time frame: assessed prior to, throughout, and following the duration of a graded exercise test, over an expected average of 2 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01538693, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2015.

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