Trial | NCT01484184  Report issue

Title

Study to Assess Safety, Tolerability and MTD of a Central Pattern Generator-activating Tritherapy (SPINALON) in Patients With Chronic Spinal Cord Injury
Tri-therapy (SPINALON)-Elicited Spinal Locomotor Network Activation: Phase I-IIa Clinical Trial in Patients With Chronic Spinal Cord Injury

  • Phase

    Phase 1/Phase 2

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    50
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.
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).
Study Started
Jul 31
2013
Primary Completion
Aug 31
2015
Study Completion
Aug 31
2015
Last Update
Aug 20
2015
Estimate

Drug SPINALON (buspirone + levodopa + cardidopa)

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 names: Apo-Buspirone 10 mg tablets (DIN 02211076), Sinemet 100/25 mg tablets (DIN 00513997)

buspirone or levodopa/carbidopa Active Comparator

Another 2-arm design will be tested composed of 16 subjects receiving drug A or drug B at MTD dose of the combined study drug as identified in the previous 2-arm groups.

Placebo Placebo Comparator

First, a 2-arm design will be used, the first arm being composed of 3 subjects receiving the lowest dose of SPINALON, the second arm being composed of 1 subject receiving a placebo. This 2-arm design will be repeated consecutively with increasing doses, as long as the dose is well tolerated. Six (6) groups are expected to be tested with this 2-arm design.

Criteria 

Inclusion Criteria:

Clinical diagnosis of complete or motor-complete SCI (ASIA-A, ASIA-B)
Chronically injured (at least 3 months post-injury)
Paraplegic (within T1-T12) or tetraplegic (within C3-C8)
In relatively good health condition (no significant bed sore, urinary tract infection)
18-65 years of age
Men and women
Quebec Province residents only

Exclusion Criteria:

With unclear diagnosis
Displayed a form of involuntary rhythmic leg muscle activity (restless leg syndrome, spontaneous activity in supine position, etc.) in the last 3 months prior to this study.
Acute or subacute stage (within 1 day and 3 months post-injury)
Non-traumatic (e.g., multiple sclerosis, syringomyelia, spinal tumor,etc.)
Are given monoamine oxidase (MAO) inhibitors (two weeks prior and after Spinalon administration)
Had seizures
Had tumor(s) (malignant or non-malignant) or in situ carcinoma in the last five (5) years
Allergic or hypersensitive to buspirone, levodopa or carbidopa
Can not take sympathomimetic amines (e.g., epinephrine, pseudoephedrine)
Currently suffering of heart problems, blood related diseases, endocrine disease, liver disease, lung disease, or kidney disease
Receiving antihypertensive drugs
Receiving tricyclic antidepressant
Receiving dopamine D2 receptor antagonists (e.g., phenothiazines, butyrophenones, risperidone)
Receiving phenytoin and papaverine
With glaucoma
With psychiatric or mental disorder(s)
Had gastrointestinal ulcer(s) in the last five (5) years
Pregnant or lactating woman (all women between 18 and 50 year-old not yet confirmed as pregnant, will be tested (urine test - TestPak Plus, Abbott Laboratories) on medical exam-day due to the teratogenic potential of levodopa/carbidopa.
Children (younger than 18 year-old) or elderly (older than 65 year-old)
Not resident of Quebec Province
No Results Posted