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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how a combination of 5-HTP (5-Hydroxytryptophan) and carbidopa affects movement and nerve activity in people with spinal cord injuries. Participants will receive varying doses of the treatment or a placebo to determine the most effective option. The trial seeks individuals who sustained a spinal cord injury at least six months ago and continue to face challenges. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of 5-HTP and carbidopa is generally well-tolerated. One study found that participants taking this combination experienced improved strength, particularly in cases involving spinal cord issues, with no serious side effects reported.

5-HTP is a substance the body produces from tryptophan, an amino acid found in foods, and is often used in dietary supplements. Carbidopa helps more 5-HTP reach the brain by preventing its breakdown.

Previous patients have demonstrated that using these together can be safe. This trial is in advanced stages, indicating some evidence of safety. However, like any treatment, participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for spinal cord injury focus on reducing inflammation or repairing nerve damage, such as corticosteroids or surgical interventions. But the combination of 5-Hydroxytryptophan (5-HTP) and carbidopa works differently by potentially enhancing serotonin synthesis, which might improve nerve signaling and function. Researchers are excited about this approach because it targets neurotransmitter pathways differently than current treatments, which could lead to improved motor recovery and quality of life for patients. This new mechanism of action offers hope for more effective recovery strategies beyond the standard care options available today.

What evidence suggests that this trial's treatments could be effective for spinal cord injury?

This trial will evaluate the effects of different treatments on movement in people with spinal cord injuries. Participants may receive a combination of 5-Hydroxytryptophan (5-HTP) and carbidopa. Research suggests this combination may improve movement by increasing serotonin levels, potentially enhancing muscle function. Earlier studies found that this combination strengthened muscles in those with severe spinal cord damage. Other participants may receive carbidopa alone or a placebo. These findings suggest possible benefits for movement in people with spinal cord injuries. ^{1 2 3 6 7}

Who Is on the Research Team?

Jessica D'Amico, PhD

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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]

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04520178

Effects of 5HTP on the Injured Human Spinal Cord

This study will assess how the serotonin precursor, 5-HTP, alter nervous system excitability and motor function in individuals with spinal cord injuries of ...

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/28566180/

Improved strength on 5-hydroxytryptophan and carbidopa ...

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

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0022510X17302903

Improved strength on 5-hydroxytryptophan and carbidopa ...

Serotonergic enhancement can benefit motor function in severe spinal cord atrophy. Abstract. There is ample evidence of an important role of ...

4.

withpower.com

withpower.com/trial/phase-2-and-3-spinal-cord-injuries-6-2020-43f48

5-HTP + Carbidopa for Spinal Cord Injury (5-HTP only 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 ...

5.

wingsforlife.com

wingsforlife.com/uk/research/effects-of-the-serotonin-precursor-5-hydroxytryptophan-5-htp-4409

Effects of the Serotonin Precursor, 5-Hydroxytryptophan (5-HTP)

Ingestion of 5-HTP will increase spinal excitability and facilitate muscle activity during a rhythmic, locomotor task, most likely through an increase in 5HT ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0753332224015737

Acute effects of L-DOPA/carbidopa/buspirone (Spinalon™) ...

Our study aims at characterizing the effects of Spinalon™ on electrical activity of the spinal cord in segmental areas known to contain key rhythmogenic ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7796270/

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis ...

5-HTP is both a drug and a natural component of some dietary supplements. 5-HTP is produced from tryptophan by tryptophan hydroxylase (TPH), which is present ...