Cyproheptadine and Chlorpromazine Effects on Spasticity

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Alberta
ClinicalTrials.gov Identifier:
NCT01509885
First received: January 10, 2012
Last updated: November 16, 2012
Last verified: November 2012
  Purpose

The main goal of this research is to understand the neuronal mechanisms that mediate the development of spasticity and motor dysfunction after spinal cord injury. The investigators examine how neurons and neuronal circuits in an injured nervous system adapt to produce the uncontrolled and unwanted muscle contractions that affect the majority (80%) of patients with spinal cord injury. One of the neurons that the investigators study is the motoneuron that excites the muscles of the limbs to produce movement. Previously, the investigators have shown that after spinal cord injury, the excessive and uncontrolled activity of motoneurons during muscle spasms is mediated, in large part, by the activation of calcium currents in the human motoneuron. In human patients the investigators have used recordings from single muscle fibres to estimate the contribution of these calcium currents in activating the motoneuron during muscle spasms. In this proposal, the investigators study why motoneurons recover these calcium currents and self-sustained activity after chronic spinal cord injury. Because the calcium currents require the presence of the monoamine serotonin (5HT) to activate, and this monoamine is greatly reduced after injury, the investigators examine if the calcium currents recover because the 5HT receptors become spontaneously active without the need for 5HT to bind to the receptor, which the investigators hypothesize to be one of the causes of spasticity after spinal cord injury. This research will pave the way to develop new pharmacological and rehabilitative therapies to both control spasticity after spinal cord injury and augment residual motor movements.


Condition
Spinal Cord Injuries
Muscle Spasticity

Study Type: Observational
Official Title: Phase 3 Study of Cyproheptadine and Chlorpromazine Effects on Spasticity After Spinal Cord Injury

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • Cutaneomuscular Reflex Responses [ Time Frame: Change after drug intake at baseline, 30minutes, 60minutes, 90minutes and 120minutes ] [ Designated as safety issue: No ]
    Tibialis anterior reflex responses evoked by stimulation of the medial arch of the foot will be measured before and after drug administration.

  • Paired motor unit recordings [ Time Frame: Change at baseline and 30, 60, 90 and 120min after drug intake ] [ Designated as safety issue: No ]
    We obtain paired motor unit recordings to determine changes in neuronal excitability after drug intake in incomplete spinal-cord injured subjects only.


Secondary Outcome Measures:
  • Blood pressure and Heart rate [ Time Frame: Change at baseline and 30, 60, 90, 120 minutes after drug intake ] [ Designated as safety issue: Yes ]
    We measure blood pressure and heart rate to determine the safety of the drug during the experiment and whether we can continue safely.


Enrollment: 20
Study Start Date: July 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Complete Spinal Cord Injured Subjects
Patients with no motor scores in their legs and suffering a complete spinal cord injury.
Incomplete Spinal Cord Injured Subjects
Patient with some motor preservation below the injury and suffering an incomplete spinal cord injury.

  Eligibility

Ages Eligible for Study:   17 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Spinal Cord Injury Patients

Criteria

Inclusion Criteria:

Patients must have suffered a trauma to the spinal cord at least 6 months ago or longer. In addition, subjects must exhibit some degree of spasticity as determined by having an Ashworth Spasticity Score, as assessed by a physical therapist, greater than 1.

Exclusion Criteria:

  • If patients have damage to the nervous system other than to the spinal cord
  • Pregnant women
  • Elderly Patients and debilitated patients
  • Alcoholic Patients
  • Patients with:

    • Known or suspected allergy to the medication or its ingredients
    • Cardiovascular disease
    • Hypotension
    • Coronary artery disease
    • Reduced liver or kidney function
    • Comatose or depressed states due to CNS depressants
    • Blood dyscrasias
    • Bone marrow depression
    • History of seizures
    • Respiratory problems
    • Hypocalcemia
    • Monoamine oxidase inhibitor therapy
    • Angle-closure glaucoma
    • Stenosing peptic ulcer
    • Symptomatic prostatic hypertrophy
    • Bladder neck obstruction
    • Pyloroduodenal obstruction
    • History of bronchial asthma
    • Increased intraocular pressure
    • Hyperthyroidism
    • Cardiovascular disease
    • Hypertension
  • Patients taking:

    • Amphetamines
    • Antihistamines-second generation
    • Anticonvulsants
    • Anticholinergics
    • CNS depressants
    • Antidepressants
    • Hypotensive agents
    • Levodopa
    • Lithium
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01509885

Locations
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G2R3
Sponsors and Collaborators
University of Alberta
Investigators
Principal Investigator: Monica A Gorassini, PhD University of Alberta
  More Information

Additional Information:
Publications:
Responsible Party: University of Alberta
ClinicalTrials.gov Identifier: NCT01509885     History of Changes
Other Study ID Numbers: Pro00020682
Study First Received: January 10, 2012
Last Updated: November 16, 2012
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Additional relevant MeSH terms:
Muscle Spasticity
Spinal Cord Injuries
Wounds and Injuries
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinal Cord Diseases
Central Nervous System Diseases
Trauma, Nervous System
Cyproheptadine
Chlorpromazine
Anti-Allergic Agents
Therapeutic Uses
Pharmacologic Actions
Antipruritics
Dermatologic Agents
Gastrointestinal Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Serotonin Antagonists
Serotonin Agents
Antiemetics

ClinicalTrials.gov processed this record on July 28, 2014