Study to Assess Safety, Tolerability and MTD of a Central Pattern Generator-activating Tritherapy (SPINALON) in Patients With Chronic Spinal Cord Injury
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Wounds and Injuries
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      As a first-in-class (Central Pattern Generator or CPG activator) approach, this tritherapy
      candidate called SPINALON has been identified and is currently under development for its
      capacity to temporarily induce episodes of involuntary locomotor movements. The primary
      objective of this Phase I/IIa study is to assess safety and tolerability of a single
      escalating dose of SPINALON (levodopa + carbidopa + buspirone) in chronic spinal cord-injured
      patients. As a secondary objective, preliminary evidence of efficacy will also be sought.
    

Detailed description: 
      Spinal cord injury (SCI) is generally considered as an irreversible condition for which no
      curative treatment has yet been found. A recent study sponsored by the Christopher & Dana
      Reeve Foundation revealed an incidence ranging between 40 and 60 cases per million population
      and a prevalence estimated to be several times greater (new data: 1,275,000 cases) than
      previously reported(previous data: 200,000 cases).

      SPINALON (levodopa + carbidopa + buspirone) was discovered by Dr. Guertin and colleagues as a
      drug treatment candidate that can acutely elicit temporarily (lasting approximately 30-60
      minutes) episodes of CPG activity and corresponding powerful weight-bearing hindlimb stepping
      in completely SCI subjects (preclinical efficacy data obtained from mice and turtles
      completely spinal cord transected thoracically).

      As such, SPINALON is currently being developed to become a chronic treatment (physical
      activity-based approach driven pharmacologically) against the multiple health problems or
      so-called 'secondary complications' associated specifically with the lack of physical
      activity (sarcopenia, osteoporosis, cardiovascular problems, dyslipidemia, obesity, type II
      diabetes, anemia, immune system deficiency, deep vein cloth, depression, etc.).

      This study is a randomized, placebo-controlled, double-blind, single dose escalation study
      with fifty-one (51) patients who will receive either placebo capsules(starch) or capsules
      with buspirone only, levodopa/carbidopa only or buspirone/levodopa/carbidopa (SPINALON).
    

Intervention name(s): SPINALON (buspirone + levodopa + cardidopa)
Intervention type(s): Drug
Intervention description(s): The proposed study is a combination of 1 and 2-arm designs. First, a 2-arm design will be used, the first arm being composed of 3 subjects receiving the lowest dose of the study drug, and the second arm being composed of 1 subject receiving a placebo. This 2-arm design will be repeated consecutively (not simultaneously) with increasing doses of SPINALON, as long as the dose is well tolerated. Six (6) groups are expected to be tested with this 2-arm design.This will be followed by a 2-arm composed of 1 group with 1 subject receiving placebo and 1 larger group (10 subjects) who will receive SPINALON at MTD as identified in the previous 2-arm groups.
Other intervention name(s): Apo-Buspirone 10 mg tablets (DIN 02211076); Sinemet 100/25 mg tablets (DIN 00513997)
Intervention MeSH terms: Levodopa; Buspirone
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Completely paralyzed; Chronically injured; Central Pattern Generator; Locomotion; Secondary complications; Activity-based training; Treadmill training; Spinal cord injury; Paraplegia; Tetraplegia