L-Dopa for Late-Life Depression

(D3 Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Warren Taylor, MD,MHSc

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Vanderbilt University Medical Center

Must not be taking: Antipsychotics, Mood stabilizers, Antidepressants

Disqualifiers: Substance abuse, Psychosis, Neurological disorder, Suicidality, others

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests L-DOPA, a medication that increases dopamine levels in the brain. It targets elderly individuals with depression who have issues with motivation, thinking speed, and movement. By boosting dopamine, the treatment aims to improve mood, cognitive function, and mobility. L-DOPA is used to treat the motor symptoms associated with Parkinson's disease by increasing dopamine levels in the brain.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude those currently or recently (within the past 2 weeks) treated with antipsychotics or mood stabilizers, or those using antidepressants where stopping is not advisable.

What evidence supports the effectiveness of the drug L-Dopa for treating late-life depression?

The research shows that L-Dopa, when combined with carbidopa as in Sinemet, is effective in treating Parkinson's disease by improving symptoms like rigidity and movement difficulties. While this is not direct evidence for treating depression, the improvement in quality of life and reduction in symptoms for Parkinson's patients suggest potential benefits for mood-related conditions. ^{1 2 3 4 5}

Is L-Dopa safe for humans?

L-Dopa, often combined with Carbidopa as Sinemet, has been used safely in humans for conditions like Parkinson's disease. Common side effects include movement issues, low muscle tone, and stomach or mental symptoms, but these rarely require stopping treatment. Long-term studies show no unexpected side effects, and it is generally well-tolerated. ^{1 6 7 8 9}

How is the drug L-Dopa unique for treating late-life depression?

L-Dopa, commonly used for Parkinson's disease, is unique for treating late-life depression because it targets dopamine levels in the brain, which may be different from standard antidepressants that typically focus on serotonin or norepinephrine. This approach could offer a novel mechanism of action for patients who do not respond to traditional treatments. ^{1 2 8 10 11}

Research Team

Warren Taylor, MD,MHSc

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for adults aged 60 or older with late-life depression, who have slower mental processing or walking speed. They must be able to consent and follow the study's procedures. Excluded are those at high suicide risk, allergic to L-DOPA, recently on certain psychiatric meds, with mobility issues due to joint/spine problems, major neurological disorders like dementia or Parkinson's, unstable illnesses, substance abuse within a year, or other primary psychiatric conditions.

Inclusion Criteria

Your depression score on the MADRS scale is 15 or higher.

I walk slower than average or think slower than others my age.

I have been diagnosed with a form of depression.

Exclusion Criteria

You have a history of severe mental health conditions like psychosis, mania, or bipolar disorder. However, if your main issue is depression and you have other mental health conditions, you may still be eligible.

History of significant radioactivity exposure (nuclear medicine studies or occupational exposure)

I am currently on or recently stopped taking medication for mental health.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Evaluation

Baseline assessments including PET imaging, MRI, neuropsychological evaluation, and mobility assessments

1-2 weeks

1-2 visits (in-person)

Treatment Phase 1

Participants receive either L-DOPA or placebo for 3 weeks, followed by assessments

3 weeks

Weekly visits (in-person)

Crossover Treatment Phase

Participants switch to the opposite intervention (L-DOPA or placebo) for another 3 weeks, followed by assessments

3 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• L-Dopa (Dopamine Precursor)
• Placebo (Drug)

Trial Overview The study tests whether carbidopa/levodopa (L-DOPA), which enhances dopamine in the brain can improve symptoms of depression by speeding up thinking and movement in older adults. Participants will either receive L-DOPA or a placebo without active ingredients to compare effects.

Participant Groups

Group I: L-Dopa First / Placebo Second Experimental Treatment 2 Interventions

STEP 1(3 weeks): Participants initially assigned to L-DOPA will begin with a Week 1 L-DOPA daily dosage of 150mg, (1.5 25mg carbidopa/100mg levodopa capsules) at 9am. Week 2 will increase to a L-DOPA daily dose of 300mg (1.5 25mg carbidopa/100mg levodopa capsules) at 9am and 5pm, followed by a Week 3 L-DOPA daily dose of 450mg (1.5 25mg carbidopa/100mg levodopa capsules) three times daily. After completing post-trial assessments, participants then enter a 1 week taper period before proceeding to Step 2. Step 2 (3 Weeks): Participants will receive matching placebo capsules daily. Participants take placebo capusles once daily during week 1 (9am), twice daily during week 2 (9am, 5pm), and three times daily during week 3 (9am, 1pm, 5pm) over three weeks. Following post-trial assessments, participants then enter a 1-week taper period and study drug is withdrawn.

Group II: Placebo First / L-Dopa Second Placebo Group 2 Interventions

Step 1 (3 Weeks): Participants will receive matching placebo capsules daily. Participants take placebo capsules once daily during week 1 (9am), twice daily during week 2 (9am, 5pm), and three times daily during week 3 (9am, 1pm, 5pm) over three weeks. Following post-trial assessments, participants then enter a 1-week taper period before proceeding to Step 2. Step 2 (3 Weeks): Participants will begin with a Week 1 L-DOPA daily dosage of 150mg, (1.5 25mg carbidopa/100mg levodopa capsules) at 9am. Week 2 will increase to a L-DOPA daily dose of 300mg (1.5 25mg carbidopa/100mg levodopa capsules) at 9am and 5pm, followed by a Week 3 L-DOPA daily dose of 450mg (1.5 25mg carbidopa/100mg levodopa capsules) three times daily. After completing post-trial assessments, participants then enter a 1 week taper period and study drug will be discontinued.

L-Dopa is already approved in Canada, Japan for the following indications:

Approved in Canada as Carbidopa/Levodopa for:

• Parkinson's disease
• Restless legs syndrome

Approved in Japan as Carbidopa/Levodopa for:

• Parkinson's disease

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

Rutgers University

Collaborator

Trials

127

Recruited

2,814,000+

Dr. Carolyn Seyss

Rutgers University

Chief Medical Officer since 2023

PharmD

Dr. Joseph A. Barone

Rutgers University

Chief Executive Officer since 2016

PharmD, FCCP

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

David Apelian

University of Pittsburgh

Chief Executive Officer since 2019

PhD in Molecular Biology from Rutgers University, MD from the University of Medicine and Dentistry of New Jersey, MBA from Quinnipiac University

Pamela D. Garzone

University of Pittsburgh

Chief Medical Officer

PhD in Clinical Science from the University of Pittsburgh

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Leslie C. Davis

University of Pittsburgh Medical Center

Chief Executive Officer since 2021

BA in Economics from Wesleyan University, MBA in Health Administration from The Wharton School

Don Yealy

University of Pittsburgh Medical Center

Chief Medical Officer since 2023

MD from the Pritzker School of Medicine, University of Chicago

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Dr. Katrina Armstrong

Columbia University

Chief Executive Officer

MD from Johns Hopkins University, MS in Epidemiology from Harvard School of Public Health

Dr. Katrina Armstrong

Columbia University

Chief Medical Officer

MD from Harvard Medical School

Emory University

Collaborator

Trials

1,735

Recruited

2,605,000+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

Findings from Research

Levodopa/carbidopa intestinal gel infusion is a viable long-term treatment option for advanced Parkinson's disease, with a median treatment duration of 3.4 years and some patients remaining on treatment for nearly 8 years.

The most common reason for discontinuation of the treatment was device-related problems, highlighting the importance of device reliability in the long-term management of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson's disease. Nyholm, D., Klangemo, K., Johansson, A.[2015]

In a study of 38 patients with Parkinson's syndrome, Madopar (a combination of L-dopa and a peripheral decarboxylase inhibitor) showed clinical improvement in about 67% of patients, particularly in reducing bradykinesia and rigidity, although tremor improvement was minimal.

Side effects were observed in approximately 40% of patients, but they were generally mild and temporary, with the main contraindications being psychotic disturbances; Madopar also enhanced the effectiveness of long-term L-dopa treatment in patients receiving it as an adjunct therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of parkinsonism with L-dopa and peripheral decarboxylase inhibitor]. Dowzenko, A., Buksowicz, C., Kuran, W.[2015]

In a study of 18 patients with Parkinson's disease, Sinemet (L-dopa and carbidopa) was found to provide the same therapeutic benefits as L-dopa alone but at lower doses and with fewer side effects.

Both Sinemet and L-dopa were most effective in reducing bradykinesia and muscular rigidity, while their impact on tremors was less pronounced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison between results achieved by administering L-dopa and Sinemet in parkinsonism in the light of our records]. Szulc-Kuberska, J., Niewodniczy, A., Poźniak-Patewics, E., et al.[2019]

In a 39-week study involving 423 patients with early Parkinson's disease, levodopa/carbidopa/entacapone (LCE) showed a statistically significant improvement in overall symptoms compared to levodopa/carbidopa (LC), with a mean difference of 1.7 points on the Unified Parkinson's Disease Rating Scale (UPDRS).

LCE also demonstrated greater benefits in daily living activities and patient-reported outcomes without increasing the risk of motor complications like dyskinesia, although it was associated with more frequent nausea and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson's disease. Hauser, RA., Panisset, M., Abbruzzese, G., et al.[2022]

In an open-label study involving eight patients with Parkinson's disease, selegiline was found to have several side effects, particularly in elderly patients.

Urinary retention occurred in two patients, highlighting the need for caution when prescribing selegiline as an adjunct treatment for Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of selegiline (Eldepryl). Waters, CH.[2019]

A clinical trial involving 587 patients with early Parkinson's disease compared the effects of L-Dopa monotherapy with a peripheral decarboxylase inhibitor to a combination therapy of L-Dopa and bromocriptine, showing that early combination therapy may help mitigate adverse effects like dyskinesia.

The trial emphasized the importance of monitoring motor performance and adverse events over a 54-month period, indicating that combining dopamine agonists with L-Dopa could enhance treatment outcomes for Parkinson's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bromocriptine lessens the incidence of mortality in L-dopa-treated parkinsonian patients: prado-study discontinued. Przuntek, H., Welzel, D., Blümner, E., et al.[2019]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Treatment of Parkinson's disease with the combination drug L-carbidopa/L-dopa. Report on a 2 years study]. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson's disease. [2015]

3. Poland pubmed.ncbi.nlm.nih.gov

[Treatment of parkinsonism with L-dopa and peripheral decarboxylase inhibitor]. [2015]

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

Sinemet and the treatment of Parkinsonism. [2019]

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

A double-blind comparison of levodopa, Madopa, and Sinemet in Parkinson disease. [2019]

6. Poland pubmed.ncbi.nlm.nih.gov

[Comparison between results achieved by administering L-dopa and Sinemet in parkinsonism in the light of our records]. [2019]

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

Long-term evaluation of Sinemet CR in parkinsonian patients with motor fluctuations. [2019]

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

Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson's disease. [2022]

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

Side effects of selegiline (Eldepryl). [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Bromocriptine lessens the incidence of mortality in L-dopa-treated parkinsonian patients: prado-study discontinued. [2019]

11. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The use of the Sinemet-CR preparation in treating Parkinson's disease]. [2016]