Effects of Baclofen on Presynaptic Inhibition in Humans

• ClinicalTrials.gov Identifier: NCT04471714
• Recruitment Status: Withdrawn
• First Posted: July 15, 2020
• Last Update Posted: April 7, 2022
• Sponsor: University of Alberta
• Information provided by (Responsible Party): University of Alberta

Study Description

Brief Summary:

This study examines the role of the GABA-B receptor in long-lasting presynaptic inhibition of primary afferents in human participants. Participants will come in for two visits, receiving baclofen (a GABA-B receptor agonist) on one visit and a placebo during the other. Electro-physiological measures will be use during both visit to asses presynaptic inhibition.

Condition or disease	Intervention/treatment	Phase
Spasticity, Muscle; Spinal Cord Injuries	Drug: Baclofen	Phase 2

Detailed Description:

The ability to execute purposeful movements relies on sensory information coming from the body. This sensory information tells us where are limbs are in relation to the rest of our body (posture sense), how fast they are moving (kinesthetic sense), how forcefully we are making a contraction (muscular sense) and if we are being contacted by external objects, changes in temperature, pain, etc (somatic sense). Without these senses, the investigators could not make well-controlled movements or navigate in our environment safely. Because of the importance of these sensory inputs, the nervous system has designed a highly regulated system to control the amount and quality of sensory inflow entering into both the spinal cord and brain. The investigators wish to re-investigate how sensory pathways from our body controls the inflow of sensory inputs in adults with and without neurological injury. Specifically, the investigators want to test if the long-lasting suppression of sensory inflow by other sensory nerves is regulated by GABA-B receptors. The investigators will test this by giving participants the GABA-B receptor agonist baclofen. Nerve stimulation and muscle responses will be used to understand how sensory transmission is being controlled in the spinal cord and the GABA-B receptors involvement. Results from these studies will provide important fundamental information about how normal sensory inflow is controlled so that the investigators can better understand how it may be altered after injury to the brain and spinal cord. This information will open new avenues of study into the treatment of sensory-related dysfunction such as spasticity and motor incoordination that occurs after central nervous system injury or disease.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: This is a double blinded, cross-over, retrospective cohort design where the size of the H-reflex and motor unit firing rates will be examined before and after oral intake of baclofen or placebo.
• Masking: Double (Participant, Investigator)
• Masking Description: Participants and researchers will be blinded. The research technician will be not be blinded
• Primary Purpose: Basic Science
• Official Title: Effects of Baclofen on Presynaptic Inhibition in Humans
• Actual Study Start Date: January 10, 2020
• Actual Primary Completion Date: March 17, 2022
• Actual Study Completion Date: March 17, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Control; Control participants will come in for two visits. In a randomized manor, they will receive baclofen on one visit and a placebo on the other.	Drug: Baclofen; Participants will come in for two visits. In a randomized manor, they will receive baclofen on one visit and a placebo on the other. During each visit the soleus H-reflex will be measured and conditioned by common peroneal nerve stimulation to assess presynaptic inhibition.; Other Name: Placebo
Experimental: Spinal Cord Injury; Participants with a spinal cord injury will come in for two visits. In a randomized manor, they will receive baclofen on one visit and a placebo on the other.	Drug: Baclofen; Participants will come in for two visits. In a randomized manor, they will receive baclofen on one visit and a placebo on the other. During each visit the soleus H-reflex will be measured and conditioned by common peroneal nerve stimulation to assess presynaptic inhibition.; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. The effects of baclofen (GABA-B) on Presynaptic Inhibition of primary afferents [ Time Frame: 1 year ]
   Our primary objective is to determine how activation of GABA-B receptors control transmission of sensory afferents as measured by the H-reflex.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy adults between the ages of 18 and 65 years.
• General good health

Exclusion Criteria:

• Contraindications to baclofen such as a known hypersensitivity to baclofen, renal impairment, stroke, epilepsy, pregnancy and lactation.
• Injury to peripheral nerves or muscles. Injury to nerves or muscles will confound the interpretation of the spinal reflex data.
• Participants with spinal cord injury already taking oral baclofen to manage spasticity.

Contacts and Locations

Locations

Canada, Alberta

524 HMRC, University of Alberta

Edmonton, Alberta, Canada, T6G2R3

Sponsors and Collaborators

University of Alberta

Investigators

• Principal Investigator: Monica Gorassini, PhD; University of Alberta

More Information

• Responsible Party: University of Alberta
• ClinicalTrials.gov Identifier: NCT04471714
• Other Study ID Numbers: Pro00090588
• First Posted: July 15, 2020
• Last Update Posted: April 7, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual participant data will be available to other researchers upon that researchers request.
• Time Frame: Upon completion of the study (TBD).
• Access Criteria: IPD will be provided to researchers who have contacted the primary investigator and requested additional data. All data will be de-identified.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Muscle Spasticity; Spinal Cord Injuries; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Baclofen; Muscle Relaxants, Central; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents; GABA-B Receptor Agonists; GABA Agonists; GABA Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action