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Completed

NCT Number: NCT01484184

Study to Assess Safety, Tolerability and MTD of a Central Pattern Generator-activating Tritherapy (SPINALON) in Patients With Chronic Spinal Cord Injury

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.

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Key information

Conditions

Spinal Cord Injury Central Nervous System Diseases Nervous System Diseases Neurologic Manifestations Paralysis Paraplegia Pathological Conditions, Signs and Symptoms Quadriplegia Signs and Symptoms Spinal Cord Diseases Spinal Cord Injuries Trauma, Nervous System Wounds and Injuries

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

McGill University Health Centre (Montreal General Hospital)

Montreal, Quebec, H3G 1A4, Canada

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

SPINALON (buspirone + levodopa + cardidopa)

Drug

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)

Primary outcomes

  1. Heart rate

    Time frame: Steadily during 4 hours post-single administration vs pre-administration

    Heart rate as a safety measure will be measured as beats per minute during 4 hours post-administration during the only administration

  2. Tolerability of common AEs

    Time frame: During 4 hours post-single administration vs pre-administration

    Frequent AEs such as nausea and hypotension will be specifically measured to assess tolerability and maximum tolerated dose. No more than 20% of subjects experiencing nausea with > grade 2 severity. Dose schedule without ≥ grade 3 hypotension. No potentiation of other AEs possibly found for each molecule administered separately

  3. Pharmacokinetics

    Time frame: 15, 30, 60, 120 and 240 min post-administration vs pre-administration

    Blood samples will be repeatedly obtained post-administration on the day of testing. HPLC analysis will be conducted to assess typical PK values (Cmax, Tmax, AUC) in order to determine whether or not the known PK profile of each active molecule (levodopa, carbidopa, buspirone) is changed once administered concomitantly (SPINALON)

  4. Blood pressure

    Time frame: During 4 hours post-single administration vs pre-administration

    Systolic and diastolic blood pressure values as a safety measure will be measured as mmHg during 4 hours

  5. Respiration rate

    Time frame: During 4 hours post-single administration vs pre-administration

    Respiration rate as number per minute will be measured as a safety issue during 4 hours post-administration compared with baseline value pre-administration on the day of testing

  6. Oxygen saturation

    Time frame: During 4 hours post-single administration vs. pre-administration

    Oxygen saturation measured as CO2 level and O2 level in percentage will be measured on the day of testing during 4 hours post-administration compared with baseline level (pre-administration)

  7. Temperature

    Time frame: During 4 hours post-single administration vs. pre-administration

    Temperature measured in degrees Celsius will be measured during 4 hours post-administration on the day of testing compared with baseline value (pre-administration)

  8. Change in hematology and biochemistry laboratory parameters

    Time frame: Once at 4 hours post-single administration vs pre-administration

    Blood samples at 4 hours post-administration will be analyzed for standard hematology (CBC) and biochemistry (liver and kidney markers) values and compared with baseline values (medical exam day sample).

Secondary outcomes

  1. Occurrence of rhythmic leg EMGs

    Time frame: During 2 hours post-administration vs pre-administration

    EMG activities of leg muscles will be measured with surface electrodes during 2 hours post-administration on the day of testing compared with baseline values pre-administration. Possible occurrence of involuntary rhythmic and bilateral movements assessed quantitatively will be sought.

Sponsors and collaborators

Lead sponsor

Nordic Life Science Pipeline Inc.

Other

Collaborators

  • United States Department of Defense

Registry information

Official study title

Tri-therapy (SPINALON)-Elicited Spinal Locomotor Network Activation: Phase I-IIa Clinical Trial in Patients With Chronic Spinal Cord Injury

Important dates

Study start
2013
Primary completion
2015
Study completion
2015
First posted
Dec 2, 2011
Registry last updated
Aug 20, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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