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Improving Ventilatory Capacity in Those With Chronic High Level SCI

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05041322
Recruitment Status : Recruiting
First Posted : September 13, 2021
Last Update Posted : February 9, 2023
Information provided by (Responsible Party):
J. Andrew Taylor, Spaulding Rehabilitation Hospital

Brief Summary:
The purpose of this study is to find out if taking the drug Buspar will increase breathing capacity in individuals with spinal cord injuries.

Condition or disease Intervention/treatment Phase
Spinal Cord Injuries Drug: Buspirone Drug: Placebo Phase 2

Detailed Description:

Chemoreceptive regulatory feedback is crucial for precise ventilatory control, especially during exercise. However, individuals with high-level SCI have a reduced chemoreceptive drive to breathe. Studies have shown lesser increases in minute ventilation and mouth pressure during hypercapnia in those with tetraplegia. Peripheral factors rather than central factors appear to cause the reduction of the ventilatory response to hypercapnia. This reduced ventilatory drive may have functional impact on exercise ventilation in patients with high level SCI and enhancing ventilatory drive may improve exercise ventilation in high-level SCI.

Currently, there are no treatments to overcome these functional deficits that affect daily activity and exercise-based rehabilitation recovery. However, previous work in an animal model of SCI has found that that a serotonin agonist markedly increases respiratory responses to carbon dioxide. Treatment with a serotonin 5HT1A agonist effectively improved the ventilatory drive after both acute and chronic spinal cord injuries in rats. One potential mechanism is increased excitability of the ventral motoneurons that have survived the spinal cord injury. 5-HT1A receptors do exist on these neurons, and when activated, amplify the excitatory output. Another mechanism resides at the intercostal and abdominal muscle afferents which influence supraspinal respiratory group neurons in the brainstem and motor output to the muscles of breathing. Hence, serotonin agonists may act on neural pathways in the spinal cord responsible for transferring afferent information from intercostal muscles to supraspinal centers. Lastly, 5-HT1A receptors may also be involved in functional plasticity of neural respiratory pathways, in particular ipsilateral phrenic nerve activity. Up regulation of 5-HT1A receptors due to denervation supersensitivity could result in postsynaptic hyperresponsivity due to loss of descending input.

BuSpar/Buspirone is a serotonin 5HT1A agonist and used as an anxiolytic in humans. It does not cause sedation, has minimal effects on psychomotor performance or cognition, and has low threshold for abuse potential or dependence liability. Prior studies have found Buspirone to be well tolerated. It has been used safely in spinal cord injury, but not for respiratory purposes. (Though there is one clinical trial in process: Role of Enhancing Serotonin Receptors Activity for Sleep Apnea Treatment in Patients with SCI.) However, Buspirone up to 60 mg daily has been used to treat disturbed respiratory rhythms in multiple sclerosis, brain cancer, and brainstem infarction. Interestingly, in patients with COPD, a 14-day oral administration of buspirone (20 mg) found improved anxiety and depression as well as increased exercise tolerance with lesser sensations of dyspnea. Hence, buspirone may offer a treatment to improve hypercapnic ventilatory drive. Given that oral administration of 30 mg results in peak plasma levels at one hour and that the average elimination half life is about 2 to 3 hours, buspirone is an attractive and safe approach to exploring the ability to improve respiratory responses to exercise and/or hypercapnia exposure in those with high level spinal cord injury that limits breathing capacity.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Improving Ventilatory Capacity in Those With Chronic High Level SCI
Actual Study Start Date : November 29, 2020
Estimated Primary Completion Date : November 29, 2023
Estimated Study Completion Date : November 29, 2024

Arm Intervention/treatment
Placebo Comparator: Placebo
Subjects take placebo pills (twice a day) for 14 Days.
Drug: Placebo
Subjects take placebo pills (twice a day) for 14 Days.
Other Name: Control

Active Comparator: Buspirone

Subjects take 30 mg buspirone HCl (15 mg twice a day) for 14 Days.

Other Names:


Drug: Buspirone
Subjects take 30 mg buspirone HCl (15 mg twice a day) for 14 Days.
Other Name: BuSpar, Buspirone Hydrochloride

Primary Outcome Measures :
  1. Pulmonary Function [ Time Frame: 14 Days ]
    A change in FEV1

  2. Hypercapnic Ventilatory Response [ Time Frame: 14 Days ]
    A change in the drive to breathe with a change in carbon dioxide

  3. Sleep Quality [ Time Frame: 14 Days ]
    A change in sleep apneas

  4. Exercise Pulmonary Capacity [ Time Frame: 14 Days ]
    Change in peak oxygen consumption during exercise

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Chronic high-level SCI (at least 24-months post injury)
  • Age 18 to 50 years.
  • Medically stable
  • Spinal Cord Injury ≥T3
  • American Spinal Injury Association grade A or B or C.
  • Able to perform arm crank exercise.

Exclusion Criteria:

  • Cardiomyopathy
  • High blood pressure( >140/90 mmHg or you are taking high blood pressure medication)
  • Significant irregular heartbeat
  • Heart disease
  • Chronic lung disease (COPD, bronchitis)
  • Current use of cardioactive or antidepressant drugs
  • Family history of significant irregular heart beat or sudden cardiac death
  • Orthostatic hypotension (symptomatic fall in blood pressure >30 mmHg when upright)
  • Current grade 2 or greater pressure ulcers at relevant contact site
  • Neurological disease (stroke, peripheral neuropathy, myopathy)
  • Arm or shoulder conditions that limit ability to perform arm crank exercise
  • History of bleeding disorder, diabetes, kidney disease, cancer, other neurological disease
  • Recent weigh change (greater than 10 pounds)
  • Regular use of tobacco
  • Intrathecal baclofen pump,
  • Current use of cardioactive, antidepressant, other sedating agents
  • Suicidal ideation
  • Pregnant and/or breastfeeding women.

In addition, subjects must have no known hypersensitivity to Buspar and must not be taking a monoamine oxidase inhibitor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05041322

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Contact: Glen Picard, MA 617-758-5511
Contact: Matthew Ely, PhD 617-758-5511

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United States, Massachusetts
Spaulding Hospital Cambridge Recruiting
Cambridge, Massachusetts, United States, 02138
Contact: Glen Picard, MA    617-758-5511   
Sponsors and Collaborators
Spaulding Rehabilitation Hospital
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Responsible Party: J. Andrew Taylor, Ph.D., Director, Cardiovascular Research Laboratory, Spaulding Rehabilitation Hospital Identifier: NCT05041322    
Other Study ID Numbers: 2016P002409
First Posted: September 13, 2021    Key Record Dates
Last Update Posted: February 9, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by J. Andrew Taylor, Spaulding Rehabilitation Hospital:
Pulmonary Function Test
Buspirone Hydrochloride
Oxygen Consumption
Additional relevant MeSH terms:
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Spinal Cord Injuries
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action