Dopaminergic Therapy for Depression with Anhedonia

Overseen By Bobbi Woolwine, CCRC

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: Antidepressants, Psychotropics, NSAIDs, Statins

Disqualifiers: Autoimmune, Cancer, Cardiovascular, Psychotic, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover new treatments for people with depression who experience anhedonia (the inability to feel pleasure) and have high inflammation. Participants will receive both a placebo and various doses of Carbidopa Levodopa, a medication often used in Parkinson's disease to boost dopamine levels. The trial suits individuals diagnosed with depression who have stopped taking antidepressants and feel little pleasure in daily activities. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand how it benefits more patients.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all antidepressant or other psychotropic medications (like mood stabilizers, antipsychotics, anxiolytics, and sedative hypnotics) for at least 4 weeks before starting the trial (8 weeks for fluoxetine).

What is the safety track record for Carbidopa Levodopa?

Research has shown that Carbidopa Levodopa, a common treatment for Parkinson's disease, is generally safe. Most side effects are known and manageable. Studies have found that it can boost motivation and reduce anhedonia, or feelings of not enjoying things. This suggests it might help people with depression who also experience high inflammation and anhedonia. As an FDA-approved medication, its safety profile is well understood. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Carbidopa Levodopa for depression with anhedonia because it offers a unique approach by targeting the brain's dopamine system. Unlike standard treatments such as SSRIs and SNRIs, which primarily focus on serotonin and norepinephrine, Carbidopa Levodopa increases dopamine levels, which can directly enhance motivation and pleasure. This dopamine-targeted mechanism could potentially offer relief to patients who don't respond well to existing antidepressants, providing a new avenue for managing symptoms of anhedonia effectively.

What evidence suggests that Carbidopa Levodopa might be an effective treatment for depression with anhedonia?

Research shows that carbidopa levodopa, a treatment under study in this trial, can help treat anhedonia—a loss of interest or pleasure—in people with depression. Studies have found that levodopa, a component of this treatment, boosts motivation and reduces symptoms of anhedonia by increasing dopamine, a brain chemical associated with pleasure and reward. Evidence also suggests that repeated use of this treatment can have lasting positive effects on mood and motivation. Its approval for other conditions supports its potential effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Jennifer Felger, PhD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for men and women aged 25-55 with depression, specifically those experiencing anhedonia (loss of pleasure) and high inflammation. Participants must have a certain score on the PHQ-9 questionnaire, not be on antidepressants or other psychotropic drugs for at least 4 weeks, and have no history of significant medical conditions or substance abuse.

Inclusion Criteria

You have a score of 10 or more on the PHQ-9.

score >10 on the Patient Health Questionnaire [PHQ]-9

I am between 25 and 55 years old.

Exclusion Criteria

urine toxicology screen is positive for drugs of abuse,

pregnancy or lactation;

I am not taking NSAIDs, glucocorticoids, or statins during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive both placebo and three doses of L-DOPA in a double-blind, placebo-controlled, crossover study

6 weeks

Weekly visits for dose adjustments and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carbidopa Levodopa
• Placebo

Trial Overview The study tests Carbidopa Levodopa's effectiveness against anhedonia in depressed individuals with high inflammation. Over six weeks, participants will receive varying doses of L-DOPA and placebos in different sequences to assess changes in their condition through lab tests, assessments, neurocognitive testing, and brain scans.

How Is the Trial Designed?

Group I: Placebo followed by Carbidopa Levodopa Experimental Treatment 2 Interventions

Participants will receive first placebo, and then Carbidopa Levodopa (L-DOPA) at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day.

Group II: Carbidopa Levodopa followed by Placebo Experimental Treatment 2 Interventions

Participants will receive first Carbidopa Levodopa at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day; and then placebo.

Carbidopa Levodopa is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Approved in United States as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Approved in Canada as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Approved in Japan as Levodopa for:

• Parkinson's disease
• Dopamine-responsive dystonia
• Restless legs syndrome

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

In 1984, the average use of L-dopa-containing drugs in Sweden was 1.46 defined daily doses per 1,000 inhabitants, indicating a strong correlation with the prevalence of Parkinson's disease, the primary condition treated with these medications.

The county of Gävleborg showed an exceptionally high usage rate of 2.34 DDD per 1,000 inhabitants, prompting further investigation into local factors that may influence this increased utilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Swedish county with unexpectedly high utilization of anti-parkinsonian drugs. Aquilonius, SM., Hartvig, P.[2019]

Levodopa/carbidopa gel (Duodopa®) has been shown to significantly improve motor symptoms in advanced Parkinson's disease, with 10 out of 11 studies reporting improvements that met clinically important differences on the Unified Parkinson's Disease Rating Scale (UPDRS) III.

The treatment also enhances quality of life, as all studies assessing this aspect reported improvements that met clinically important differences, although most adverse events were related to the infusion system rather than the drug itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duodopa® treatment for advanced Parkinson's disease: a review of efficacy and safety. Nyholm, D.[2013]

Levodopa therapy revolutionized the treatment of Parkinson's disease (PD) after its effectiveness was confirmed in 1967, despite initial inconsistent results, but it also introduced significant side effects like dyskinesias and motor fluctuations.

The addition of dopa decarboxylase inhibitors, such as carbidopa, in the 1970s improved symptom control and reduced side effects, leading to more effective long-term management of PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

History of levodopa and dopamine agonists in Parkinson's disease treatment. Tolosa, E., Martí, MJ., Valldeoriola, F., et al.[2019]

In a study of 60 Parkinsonism patients, the combination of levodopa with G31,406 showed potential benefits due to its anticataleptic effects, likely linked to its anticholinergic and dopaminergic actions.

The study aimed to assess not only the efficacy of these drug combinations but also the side effects and their impact on depression commonly experienced by Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The L-dopa sparing effect of G 31,406 in the treatment of parkinson's disease. Couto, B., Oliveira, C., Mattos, JP., et al.[2013]

A study involving 20 patients with Parkinson's disease confirmed that the combination of L-dopa with a peripheral aromatic amino acid decarboxylase inhibitor (benserazide or carbidopa) is the most effective treatment available, allowing for an 80% reduction in L-dopa dosage.

Switching between the two formulations, Madopar and Sinemet, can help maintain efficacy and prevent loss of effectiveness during long-term treatment, as both achieve similar plasma levels of L-dopa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The combined treatment of Parkinson's disease with L-dopa plus decarboxylase inhibitors (carbidopa, benserazide) (author's transl)]. Podiwinsky, F., Mentasti, M., Riederer, P., et al.[2013]

Carbidopa (CD) significantly accumulates in the rat hypothalamus and striatum after administration, with peak levels observed one hour post-injection, indicating its ability to penetrate the brain and potentially influence dopamine metabolism.

At higher doses, carbidopa can inhibit dopamine formation in the brain, particularly in the hypothalamus, while also affecting the levels of other metabolites, suggesting a complex interaction between carbidopa and levodopa in the treatment of conditions like Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of systemic carbidopa on dopamine synthesis in rat hypothalamus and striatum. Kaakkola, S., Tuomainen, P., Wurtman, RJ., et al.[2019]

Levodopa is the primary treatment for Parkinson's disease, working by restoring dopamine release from damaged brain cells, which helps alleviate symptoms.

While effective, levodopa can cause side effects like dyskinesia due to its action on brain receptors, and using peripheral decarboxylase inhibitors can help reduce nausea associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of some aspects of the pharmacology of levodopa. Morris, JG.[2014]

In a study of 34 patients with advanced Parkinson's disease who were intolerant to L-DOPA, a higher proportion of carbidopa (25%) was preferred by most patients and helped reduce gastrointestinal and psychiatric side effects associated with L-DOPA.

While increasing carbidopa improved side effects, the overall improvement in disability was modest, indicating that while the combination may enhance tolerability, it does not significantly enhance the effectiveness of L-DOPA in treating Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbidopa dosage modifies L-dopa induced side effects and blood levels of L-dopa and other amino acids in advanced parkinsonism. Bermejo Pareja, F., Martinez-Martin, P., Muradas, V., et al.[2019]

Levodopa, particularly in the form of levodopa-carbidopa intestinal gel, is crucial for providing continuous dopaminergic stimulation, which is essential in the treatment of Parkinson's disease.

Studies highlight the efficacy and safety of this treatment, showing improvements in the quality of life for patients undergoing long-term therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Levodopa: the story continues]. Titova, NV., Katunina, EA.[2016]

In a study involving 29 patients with Parkinson's disease, Sinemet-CR demonstrated a high effectiveness rate of 80%, particularly improving symptoms like rigidity, hypokinesia, and tremor over a treatment duration of 3 months.

The treatment was found to be safe, with only 6 cases reporting negative side effects, supporting its recommendation for broader use in managing Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of the Sinemet-CR preparation in treating Parkinson's disease]. Artem'ev, DV., Damulin, IV., Iakhno, NN.[2016]

In a double-blind study involving 28 patients with chronic schizophrenia, L-dopa treatment (up to 1250 mg daily) showed significant improvement in symptoms according to nurse assessments, despite psychiatrist and psychologist ratings indicating only minor changes.

The study lasted six weeks and all participants continued their regular neuroleptic medication, suggesting that L-dopa may enhance treatment outcomes in schizophrenia when combined with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double blind trial of L-dopa in chronic schizophrenia. Buchanan, FH., Parton, RV., Warren, JW., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5154907/

Anhedonia Is Associated with Poorer Outcomes in ... It also tested the hypothesis that a dopaminergic drug, levodopa (L-DOPA), would improve the effectiveness of CM, particularly in individuals high in anhedonia.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0889159124007554

Sustained effects of repeated levodopa (L-DOPA) ... L-DOPA improved effort-based motivation, with preliminary effects on anhedonia and depression severity. 3.2.1. Primary behavioral outcome, objective-motivation.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06075771

NCT06075771 | Dopaminergic Therapy for Anhedonia - 2 The purpose of this 8-week, double-blind, placebo-controlled, study is to explore new treatment options for people with depression who have high inflammation ...

4. withpower.com withpower.com/trial/phase-4-anhedonia-2021-4d7e5

Dopaminergic Therapy for Depression with Anhedonia Trial Overview The study tests Carbidopa Levodopa's effectiveness against anhedonia in depressed individuals with high inflammation. Over six weeks, ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39694342/

Sustained effects of repeated levodopa (L-DOPA ... - PubMed Sustained effects on reward circuitry, effort-based motivation, and anhedonia by repeated L-DOPA administration support the therapeutic potential of agents ...