5-HTP + Carbidopa for Spinal Cord Injury
(5-HTP only Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: University of Alberta
Must not be taking: Antidepressants, Amphetamines, Lithium, others
Disqualifiers: Epilepsy, Cardiovascular disease, Psychiatric disorder, others
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
This study will assess how the serotonin precursor, 5-HTP, alter nervous system excitability and motor function in individuals with spinal cord injuries of differing chronicity and severity. Participants will visit the lab on 4 separate occasions where they will be administered four different drugs in a randomized, double-blinded, placebo-controlled crossover design.
Will I have to stop taking my current medications?
Yes, you may need to stop taking certain medications. The trial excludes participants taking specific drugs like antidepressants, amphetamines, and some blood pressure medications, among others. It's important to discuss your current medications with the trial team to see if any need to be stopped.
What evidence supports the effectiveness of the drug 5-HTP + Carbidopa for spinal cord injury?
Is 5-HTP combined with Carbidopa safe for humans?
There is limited safety data specifically for the combination of 5-HTP and Carbidopa in humans, but 5-HTP is generally considered safe when used appropriately, and Carbidopa is commonly used in combination with other medications for Parkinson's disease. However, individual responses can vary, and it's important to consult with a healthcare provider before starting any new treatment.12346
How does the drug 5-HTP + Carbidopa differ from other treatments for spinal cord injury?
Eligibility Criteria
This trial is for individuals who have had a spinal cord injury at least six months ago. It's not suitable for those with kidney or liver disease, heart issues, psychiatric disorders, epilepsy, glaucoma, blood diseases, endocrine dysfunction, stomach ulcers or those on certain medications like antidepressants and CNS depressants.Inclusion Criteria
I had a spinal cord injury more than six months ago.
I had a spinal cord injury more than six months ago.
Exclusion Criteria
I have had tumors in the past.
I have kidney problems.
Low levels of calcium in your blood.
See 32 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive different doses of 5-HTP and carbidopa or placebo in a randomized, double-blinded, placebo-controlled crossover design
4 visits, each separated by at least 72 hours
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- 5-Hydroxytryptophan (Serotonin Precursor)
- Carbidopa (Dopa Decarboxylase Inhibitor)
Trial OverviewThe study tests how 5-HTP affects nervous system activity and motor skills in people with spinal cord injuries. Participants will take four different treatments (including a placebo) across four visits in a randomized order without knowing which one they're receiving each time.
Participant Groups
4Treatment groups
Active Control
Placebo Group
Group I: High-dose 5HTPActive Control2 Interventions
100mg 5-HTP in combination with 50mg carbidopa
Group II: Low-dose 5HTPActive Control2 Interventions
50mg 5-HTP in combination with 50mg carbidopa
Group III: CarbidopaPlacebo Group1 Intervention
50mg carbidopa only
Group IV: PlaceboPlacebo Group1 Intervention
Placebo comparator
5-Hydroxytryptophan is already approved in United States for the following indications:
🇺🇸 Approved in United States as 5-HTP for:
- Anxiety
- ADHD
- Insomnia
- Headache
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Louisville, Kentucky Spinal Cord Injury Research CentreLouisville, KY
University of AlbertaEdmonton, Canada
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Who Is Running the Clinical Trial?
University of AlbertaLead Sponsor
University of LouisvilleLead Sponsor
Wings for LifeCollaborator
References
Indorenate improves motor function in rats with chronic spinal cord injury. [2013]The effect of indorenate (5-methoxytryptamine, beta-methyl carboxylate hydrochloride), a 5-HT1A agonist, was investigated on the motor performance of rats with chronic spinal cord injury. Four months after a ninth thoracic vertebrae spinal cord contusion, 29 rats were randomly allocated into two groups: saline solution and indorenate-treated animals with daily doses incremented at weekly intervals. The locomotor performance of all rats was measured by the Basso, Beattie, and Bresnahan (BBB) rating scale. The results showed that at the end of the treatment, the motor activity of indorenate group was significantly better than that presented by saline solution group. The 80% of indorenate, (against 15% of saline solution) did not show detriment on motor activity. When we analysed the motor activity of rats with basal BBB lower than 10, a significant improvement of motor recovery in indorenate-treated animals was observed. The benefits observed in locomotor function at low doses followed by increasing doses could be associated with pharmacological treatment by indorenate, a well-known 5-HT1A receptor agonist. Our results suggest a potential mechanism by which serotonergic agents may improve motor function in rats with chronic spinal cord injury.
Improved strength on 5-hydroxytryptophan and carbidopa in spinal cord atrophy. [2018]There is ample evidence of an important role of descending serotonergic projections in modulating spinal motor neuron activation and firing, and experimental studies suggest that 5-HT receptor stimulation can improve motor function after spinal cord injury; however, relevant clinical data is sorely lacking. We describe two sisters with hemiplegic migraine, low CSF and platelet serotonin levels, and progressive spastic paraparesis associated with profound spinal cord atrophy whose lower extremity strength and ambulation responded to a precursor replacement strategy (5-hydroxytryptophan and carbidopa administration), an approach that may have broader applicability in myelopathies of diverse etiology where descending serotonergic projections are compromised.
Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury. [2022]In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal.
The combination of human neuronal serotonergic cell implants and environmental enrichment after contusive SCI improves motor recovery over each individual strategy. [2013]A human neuronal cell line, hNT2.19, which secretes serotonin (5-HT) after differentiation, was used as a transplant source to improve motor dysfunction following severe contusive spinal cord injury (SCI). Also, environmental enrichment (EE) was added to the interspinal transplant treatment paradigm. Motor testing was performed weekly before and following SCI, with and without EE and/or cell transplant conditions. Motor recovery was maximal when both cell transplant and EE were used. Individual treatment paradigms also significantly improved foot rotation and reduced footfall errors but not stride length or base of support dysfunction. This recovery of motor function after SCI suggests that the combinatory use of serotonergic hNT2.19 cell grafts plus EE is a meaningful strategy to modestly improve motor dysfunction that accompanies contusive SCI.
Contribution of serotonin neurons to the functional recovery after spinal cord injury in rats. [2019]The contribution of serotonin neurons to the functional recovery after spinal cord injury was studied pharmacologically in rats with moderately severe neurologic impairment (complete paraplegia but responsive to tail pinching) 24 h after thoracic spinal cord (T11) compression-induced injury. Fourteen days after cord injury the levels of endogenous norepinephrine (NE, -33%), dopamine (DA, -50%) and serotonin (5-HT, -55%) in the lumbar cord in the injury control rats were decreased and there were significant correlations between the neurologic score and the NE level (rs = 0.562, P less than 0.01) and the 5-HT level (rs = 0.745, P less than 0.001) but not the DA level. Bilateral i.c.v. injection of 5,7-dihydroxytryptamine (200 micrograms/rat) 24 h after cord injury significantly retarded the neurologic recovery during the 14 days after injury, accompanied by a further reduction in the 5-HT level (-86%) but not in the NE or DA level. On the other hand, neither p-chlorophenylalanine (PCPA) (300 mg/kg, i.p., once daily starting 24 h after injury for 13 consecutive days) nor reserpine (1 mg/kg, i.p., 4 times, once 24 h after injury and then every fourth day) had any influence on the time course of the neurologic recovery during the 14 days after injury, although PCPA treatment further reduced the levels of NE (-50%) and 5-HT (-91%), and reserpine treatment further reduced the levels of NE (-95%), DA (-73%) and 5-HT (-85%).(ABSTRACT TRUNCATED AT 250 WORDS)
The role of the serotonergic system in locomotor recovery after spinal cord injury. [2018]Serotonin (5-HT), a monoamine neurotransmitter synthesized in various populations of brainstem neurons, plays an important role in modulating the activity of spinal networks involved in vertebrate locomotion. Following spinal cord injury (SCI) there is a disruption of descending serotonergic projections to spinal motor areas, which results in a subsequent depletion in 5-HT, the dysregulation of 5-HT transporters as well as the elevated expression, super-sensitivity and/or constitutive auto-activation of specific 5-HT receptors. These changes in the serotonergic system can produce varying degrees of locomotor dysfunction through to paralysis. To date, various approaches targeting the different components of the serotonergic system have been employed to restore limb coordination and improve locomotor function in experimental models of SCI. These strategies have included pharmacological modulation of serotonergic receptors, through the administration of specific 5-HT receptor agonists, or by elevating the 5-HT precursor 5-hydroxytryptophan, which produces a global activation of all classes of 5-HT receptors. Stimulation of these receptors leads to the activation of the locomotor central pattern generator (CPG) below the site of injury to facilitate or improve the quality and frequency of movements, particularly when used in concert with the activation of other monoaminergic systems or coupled with electrical stimulation. Another approach has been to employ cell therapeutics to replace the loss of descending serotonergic input to the CPG, either through transplanted fetal brainstem 5-HT neurons at the site of injury that can supply 5-HT to below the level of the lesion or by other cell types to provide a substrate at the injury site for encouraging serotonergic axon regrowth across the lesion to the caudal spinal cord for restoring locomotion.
Phenolic acid concentrations in the lumbar cerebrospinal fluid of Parkinsonian patients treated with L-dopa. [2019]The acid metabolites of dopamine and 5-hydroxytryptamine were estimated in the lumbar cerebrospinal fluid (CSF) of Parkinsonian patients both before and during treatment with l-dopa, the amino acid precursor of dopamine. An attempt was made to relate clinical improvement to the biochemical results. The dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, showed increases related to the dose of l-dopa, the increase in homovanillic acid concentration being proportionately greater than that of 3,4-dihydroxyphenylacetic acid. The concentration of the 5-hydroxytryptamine metabolite, 5-hydroxyindol-3ylacetic acid, was unaltered by the drug. Clinical improvement, which in the early stages was evident particularly in the bradykinesia, was found to occur at doses of l-dopa greater than 1·5 g/day. Effective doses of l-dopa gave rise to concentrations of dopamine metabolites in the CSF which were greater than normal. Possible implications of these findings are discussed.
5-Hydroxytryptophan-induced respiratory recovery after cervical spinal cord hemisection in rats. [2017]The present study investigates the role of serotonin in respiratory recovery after spinal cord injury. Experiments were conducted on C(2) spinal cord hemisected, anesthetized, vagotomized, paralyzed, and artificially ventilated rats in which end-tidal CO(2) was monitored and maintained. Before drug administration, the phrenic nerve ipsilateral to hemisection showed no respiratory-related activity due to the disruption of the descending bulbospinal respiratory pathways by spinal cord hemisection. 5-Hydroxytryptophan (5-HTP), a serotonin precursor, was administrated intravenously. 5-HTP induced time- and dose-dependent increases in respiratory recovery in the phrenic nerve ipsilateral to hemisection. Although the 5-HTP-induced recovery was initially accompanied by an increase in activity in the contralateral phrenic nerve, suggesting an increase in descending respiratory drive, the recovery persisted well after activity in the contralateral nerve returned to predrug levels. 5-HTP-induced effects were reversed by a serotonin receptor antagonist, methysergide. Because experiments were conducted on animals subjected to C(2) spinal cord hemisection, the recovery was most likely mediated by the activation of a latent respiratory pathway spared by the spinal cord injury. The results suggest that serotonin is an important neuromodulator in the unmasking of the latent respiratory pathway after spinal cord injury. In addition, the results also suggest that the maintenance of 5-HTP-induced respiratory recovery may not require a continuous enhancement of central respiratory drive.