5-HTP + Carbidopa for Spinal Cord Injury

(5-HTP only Trial)

Recruiting at 1 trial location

Overseen By Monica A Gorassini, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Alberta

Must not be taking: Antidepressants, Amphetamines, Lithium, others

Disqualifiers: Epilepsy, Cardiovascular disease, Psychiatric disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 4 visits, each separated by at least 72 hours

30 Participants Needed

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?

Research suggests that stimulating serotonin receptors can improve motor function after spinal cord injury. In one study, two sisters with spinal cord atrophy showed improved strength and walking ability after taking 5-HTP and Carbidopa, indicating potential benefits for similar conditions. ^{1 2 3 4 5}

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. ^{1 2 3 4 6}

How does the drug 5-HTP + Carbidopa differ from other treatments for spinal cord injury?

The drug 5-HTP + Carbidopa is unique because it uses a precursor replacement strategy to enhance serotonin levels, which may improve motor function and strength in spinal cord injury by stimulating serotonin receptors, a mechanism not commonly targeted by other treatments. ^{1 2 5 7 8}

Research Team

Jessica D'Amico, PhD

Principal Investigator

University of Alberta

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.

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
• Carbidopa

Trial Overview The 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

Group I: High-dose 5HTP Active Control 2 Interventions

100mg 5-HTP in combination with 50mg carbidopa

Group II: Low-dose 5HTP Active Control 2 Interventions

50mg 5-HTP in combination with 50mg carbidopa

Group III: Carbidopa Placebo Group 1 Intervention

50mg carbidopa only

Group IV: Placebo Placebo Group 1 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

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

Wings for Life

Collaborator

Trials

8

Recruited

860+

Findings from Research

Indorenate, a 5-HT1A agonist, significantly improved motor performance in rats with chronic spinal cord injury compared to a saline solution, as measured by the BBB rating scale.

The study found that 80% of the indorenate-treated rats showed no detriment in motor activity, and those with lower baseline motor function experienced notable recovery, suggesting that serotonergic agents could enhance motor function in similar injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indorenate improves motor function in rats with chronic spinal cord injury. Bravo, G., Ibarra, A., Guizar-Sahagún, G., et al.[2013]

Two sisters with hemiplegic migraine and low serotonin levels showed significant improvement in lower extremity strength and ambulation after treatment with a precursor replacement strategy using 5-hydroxytryptophan and carbidopa.

This case suggests that enhancing serotonergic signaling may be a promising therapeutic approach for improving motor function in conditions like spinal cord atrophy and other myelopathies where serotonin pathways are compromised.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved strength on 5-hydroxytryptophan and carbidopa in spinal cord atrophy. Horvath, GA., Meisner, L., Selby, K., et al.[2018]

In individuals with incomplete spinal cord injuries, the serotonin reuptake inhibitor citalopram increased reflex responses, indicating that functional monoamine receptors are active below the injury site, which may contribute to spasticity.

In contrast, in those with complete spinal cord injuries, blocking constitutive serotonin and norepinephrine receptor activity with cyproheptadine reduced muscle spasms, suggesting that targeting these receptors could be an effective strategy for managing spasticity in severe cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury. D'Amico, JM., Murray, KC., Li, Y., et al.[2022]

Transplanting a human neuronal cell line that secretes serotonin (hNT2.19) significantly improved motor function after severe spinal cord injury (SCI), especially when combined with environmental enrichment (EE).

The combination of cell transplant and EE led to the best recovery outcomes, indicating that this approach can effectively enhance motor function recovery in SCI, although it primarily improved specific aspects like foot rotation and footfall errors rather than overall stride length.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of human neuronal serotonergic cell implants and environmental enrichment after contusive SCI improves motor recovery over each individual strategy. Eaton, MJ., Pearse, DD., McBroom, JS., et al.[2013]

In a study of rats with spinal cord injury, serotonin levels were significantly correlated with neurological recovery, suggesting that serotonin plays a crucial role in functional recovery after such injuries.

Injecting a serotonin-depleting agent (5,7-dihydroxytryptamine) shortly after injury hindered recovery and drastically reduced serotonin levels, indicating that maintaining serotonin levels may be important for improving outcomes after spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contribution of serotonin neurons to the functional recovery after spinal cord injury in rats. Hashimoto, T., Fukuda, N.[2019]

After a spinal cord injury (SCI), the loss of serotonin (5-HT) and changes in its receptors can lead to significant locomotor dysfunction, including paralysis.

Various strategies, such as using 5-HT receptor agonists or cell therapies to restore serotonergic input, have shown promise in improving locomotor function by activating the central pattern generator (CPG) below the injury site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of the serotonergic system in locomotor recovery after spinal cord injury. Ghosh, M., Pearse, DD.[2018]

In Parkinsonian patients, treatment with l-dopa significantly increased the levels of dopamine metabolites in the cerebrospinal fluid, particularly homovanillic acid, which rose more than 3,4-dihydroxyphenylacetic acid, indicating a strong biochemical response to the medication.

Clinical improvements, especially in bradykinesia, were observed at l-dopa doses greater than 1.5 g/day, suggesting that higher doses are necessary for effective symptom management in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phenolic acid concentrations in the lumbar cerebrospinal fluid of Parkinsonian patients treated with L-dopa. Pullar, IA., Weddell, JM., Ahmed, R., et al.[2019]

In a study on rats with spinal cord injury, the administration of 5-hydroxytryptophan (5-HTP), a serotonin precursor, led to significant improvements in respiratory recovery, indicating serotonin's crucial role in activating latent respiratory pathways after injury.

The respiratory recovery induced by 5-HTP persisted even after the initial increase in respiratory drive returned to baseline, suggesting that ongoing stimulation of the central respiratory drive is not necessary for maintaining respiratory function post-injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-Hydroxytryptophan-induced respiratory recovery after cervical spinal cord hemisection in rats. Zhou, SY., Goshgarian, HG.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Indorenate improves motor function in rats with chronic spinal cord injury. [2013]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Improved strength on 5-hydroxytryptophan and carbidopa in spinal cord atrophy. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

The combination of human neuronal serotonergic cell implants and environmental enrichment after contusive SCI improves motor recovery over each individual strategy. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Contribution of serotonin neurons to the functional recovery after spinal cord injury in rats. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

The role of the serotonergic system in locomotor recovery after spinal cord injury. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Phenolic acid concentrations in the lumbar cerebrospinal fluid of Parkinsonian patients treated with L-dopa. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

5-Hydroxytryptophan-induced respiratory recovery after cervical spinal cord hemisection in rats. [2017]