History of Changes for Study: NCT03761030

L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	Submitted Date	Changes
1	November 29, 2018	None (earliest Version on record)
2	November 30, 2018	Outcome Measures and Study Status
3	January 15, 2019	Recruitment Status, Study Status, Study Identification, Oversight, Contacts/Locations and Study Design
4	February 5, 2019	Study Status
5	January 28, 2020	Study Status
6	March 5, 2020	Contacts/Locations, Study Status and Eligibility
7	April 15, 2020	Recruitment Status, Study Status, Contacts/Locations and Study Design
8	April 16, 2020	Recruitment Status and Study Status
9	June 18, 2020	Arms and Interventions, Eligibility, Study Design, Study Status, Study Description, Oversight and Sponsor/Collaborators
10	July 27, 2020	Recruitment Status, Study Status, Contacts/Locations and Study Design
11	April 16, 2021	Study Status
12	January 26, 2022	Recruitment Status, Study Status and Contacts/Locations
13	May 2, 2023	Quality Control Review has not concluded Returned: May 16, 2023 Recruitment Status, Study Status, Outcome Measures, Contacts/Locations, Study Design, Document Section and Study Description
14	May 17, 2023	Quality Control Review has not concluded Returned: May 18, 2023 Outcome Measures, Document Section, Baseline Characteristics and Study Status
15	May 18, 2023	Study Status, Outcome Measures

Comparison Format:

Merged
Side-by-Side

Show only changed modules

Study Identification


Unique Protocol ID:	7733
Brief Title:	L-DOPA vs. Placebo for Depression and Psychomotor Slowing in Older Adults
Official Title:	Targeting Dopaminergic Mechanisms of Slowing to Improve Late Life Depression
Secondary IDs:	NIMH R61 MH110029 [NIMH] 4R33MH110029-03 [U.S. NIH Grant/Contract]

Study Status


Record Verification:	November 2018 January 2022
Overall Status:	Not yet recruiting Suspended [This study is temporarily suspended by NIMH]
Study Start:	December 1, 2018 January 9, 2019
Primary Completion:	May December 31, 2021 2022 [Anticipated]
Study Completion:	November 30 December 31, 2021 2022 [Anticipated]

First Submitted:	November 29, 2018
First Submitted that Met QC Criteria:	November 29, 2018
First Posted:	December 3, 2018 [Actual]

Last Update Submitted that Met QC Criteria:	November 29, 2018 January 26, 2022
Last Update Posted:	December 3, 2018 [Actual] February 10, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	New York State Psychiatric Institute
Responsible Party:	Principal Investigator Investigator: Bret Rutherford Official Title: Associate Professor Associate Professor of Clinical Psychiatry Affiliation: New York State Psychiatric Institute
Collaborators:	National Institute of Mental Health (NIMH)

Oversight


U.S. FDA-regulated Drug:	No Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

Study Description

Brief Summary:

Individuals with Late Life Depression (LLD) often have cognitive problems, particularly problems with memory, attention, and problem solving, all of which contribute to antidepressant non-response. Our group and others have shown that decreased thinking speed is the central cause of functional problems in patients with LLD. Similarly, decreased walking speed is associated with depression and carries additional risk for falls, hospitalization, and death. Available evidence suggests that declining functionality in the brain's dopamine system contributes to age-related cognitive and motor slowing. The central hypothesis of this study is that by enhancing dopamine functioning in the brain and improving cognitive and motor slowing, administration of carbidopa/levodopa (L-DOPA) will improve depressive symptoms in older adults.

Detailed Description:

N=90 adults of which 30 participants will undergo scanning procedures, aged > 60 years and older with (1) a DSM 5 depressive disorder, (2) significant depressive symptoms, and (3) decreased thinking or walking speed will receive 8 weeks of treatment with L-DOPA up to 450mg. We will test whether L-DOPA increases brain dopamine release using neuroimaging and whether it speeds up thinking and walking speed. Data collected in the proposed studies may help identify a new treatment for LLD, which could have large public health ramifications given the prevalence, frequent treatment resistance, and chronicity characteristic of LLD. This project also will elucidate the neurobiology of slowing at molecular, structural, and functional levels of analysis, increasing our understanding of the interplay between these aging-associated processes and the pathophysiologic changes underlying late life neuropsychiatric disorders. Exploring patient characteristics that predict response to L-DOPA may provide useful information to guide differential therapeutics and develop personalized medicine for LLD.

Conditions


Conditions:	Major Depressive Disorder Dysthymia Depression
Keywords:	Depressive symptoms Cognitive problems Antidepressant non-response Dopamine system Older Adults Motor slowing

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Not Applicable Phase 4
Interventional Study Model:	Parallel Assignment
Number of Arms:	2
Masking:	Double Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	90 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

Experimental: L- Dopa DOPA Arm

Those assigned to L-DOPA will begin taking 37.5mg carbidopa/150 mg levodopa once daily (with placebo twice daily) for one week, then increase to 75mg carbidopa/300mg levodopa (37.5 mg carbidopa/150mg levodopa twice daily and placebo once daily) for one week, and finally increase to 112.5mg carbidopa/450mg levodopa (37.5 mg carbidopa/150mg levodopa three times daily and no placebo) for the final six weeks . . Each subject assigned to the L-DOPA arm will be titrated to 450mg L-DOPA unless they cannot tolerate higher doses, in which case subjects will have their dosage reduced to the maximum tolerable dose

Drug: L- Dopa DOPA

We will be using generic sinemet 25/100 tablets in this study.

Other Names:

carbidopa/levodopa (Sinemet)

Placebo Comparator: Placebo Arm

Subjects assigned to the placebo arm will take placebo oral tablet three times daily throughout the study.

Drug: Placebo Oral Tablet

25/100 placebo tablets

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures:

Hamilton Depression Rating Scale for Depression ( HAM-D HRSD)
[ Time Frame: 8 Weeks ]

A multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Our target is depressive symptomatology as measured by the HAM-D. Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

Eligibility


Minimum Age:	59 60 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Aged 60 years and older DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified Hamilton Rating Scale for Depression (HRSD) > 15 Decreased processing speed (defined as performance > 0.5SD below age-adjusted norms on Digit Symbol Substitution Test or Trail Making Test Part A) OR decreased gait speed (defined as average walking speed over 15' course < 1m/s) Willing to and capable of providing informed consent and complying with study procedures Alternative standard treatments for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy) have been discussed and the individual agrees to be involved in an experimental treatment. Age >59 years DSM 5 non-psychotic Major Depressive Disorder, Dysthymia, or Depression Not Otherwise Specified Center for Epidemiological Studies Depression (CES-D) Rating Scale >9 decreased processing speed (defined as performance > 0.5SD below age-adjusted norms on Digit Symbol Substitution Test or Trail Making Test Part A) OR decreased gait speed (defined as average walking speed over 15' course < 1m/s) willing to and capable of providing informed consent and complying with study procedures prefer not to be treated with a standard treatment for MDD, Dysthymia, or Depression NOS (e.g., antidepressant medication or psychotherapy). Exclusion Criteria: Diagnosis of substance abuse or dependence (excluding Tobacco Use Disorder) within the past 12 months. History of or current psychosis, psychotic disorder, mania, or bipolar disorder Diagnosis of probable Alzheimer's Disease, Vascular Dementia, or Parkinson's Disease (PD) Mini Mental Status Exam (MMSE) < 25 HRSD ≥ 28; HRSD suicide item > 2 or the presence of significant suicide risk as judged by clinician or Clinical Global Impressions (CGI)-Severity score of 7 at baseline. Current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, dopaminergic agents, or mood stabilizers. History of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA Acute, severe, or unstable medical or neurological illness Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, mobility limiting history of joint replacement surgery, or history of spine surgery FOR SUBJECTS RECEIVING PET/MRI SCANS ONLY: Having contraindication to MRI scanning (such as metal in body) or unable to tolerate the scanning procedures History of significant radioactivity exposure (nuclear medicine studies or occupational exposure) diagnosis of substance abuse history of or current psychosis, psychotic disorder, mania, or bipolar disorder diagnosis of probable Alzheimer's Disease, Vascular Dementia, or PD Mini Mental Status Exam (MMSE) < 25 HRSD ≥ 25 or the presence of significant suicide risk current or recent (within the past 4 weeks) treatment with antidepressants, antipsychotics, dopaminergic agents, or mood stabilizers history of allergy, hypersensitivity reaction, or severe intolerance to L-DOPA acute, severe, or unstable medical or neurological illness mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, mobility limiting history of joint replacement surgery, or history of spine surgery FOR SUBJECTS RECEIVING PET/MRI SCANS ONLY: having contraindication to MRI scanning (such as metal in body) or unable to tolerate the scanning procedures history of significant radioactivity exposure (nuclear medicine studies or occupational exposure)

Contacts/Locations


Central Contact Person:	Emily Valente, MS Telephone: 646-774-6704 Email: emily.valente@nyspi.columbia.edu
Central Contact Backup:	Bret R Rutherford, MD Telephone: 646774-8660 Email: brr8@cumc.columbia.edu
Study Officials:	Bret R Rutherford, MD Principal Investigator Associate Professor of Clinical Psychiatry
Locations:	United States, New York
	New York State Psychiatric Institute New York, New York, United States, 10032

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information: