Imaging the Nucleus Accumbens in Major Depressed Patients 'Treated With Pramipexole

• Sponsor: Stanford University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01066897
• Collaborator: National Alliance for Research on Schizophrenia and Depression (Other)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

We hope to learn how a brain circuit that is important to the understanding of depression, anhedonia and positive affect responds to a novel pharmaceutical treatment for depression and related symptoms. Adults who have a diagnosis of major depression and are not completely responsive to antidepressant medication will be sought out for participation; as will an equal number of adults not suffering from the disorder. Those suffering from depression will be given pramipexole, an investigational medication for eight weeks during which information will be collected about mood, cognition, and brain function. Adults not suffering from depression will also be evaluated with these measures.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Pramipexole	Phase 4

Detailed Description

Patients who meet DSM-IV criteria for major depression(using the SCID),have a Hamilton Depression Rating Scale score of at least 18, and who are not complete responders to antidepressant medications will be invited to participate in an open label study with pramipexole. Patients who are not complete responders to an adequate trial of an antidepressant (see inclusion criteria below) will be openly treated with pramipexole for 8 weeks. Participants must be between the ages of 20-55 and will include both men and women. Patient's mood will be assessed each visit using the Hamilton Depression (HDRS) and will also complete a series of questionnaires. This will include the physical and social anhedonia scales (Chapman et al., 1976; Eckblad et al., 1982), the Snaith-Hamilton Pleasure Scale (SHAPS; Franken et al., 2007; Snaith et al., 1995), the Mood and Anxiety Symptom Questionnaire Short Form (MASQ; Watson, Weber, et al., 1995; Watson, Clark, et al., 1995), and the Positive and Negative Affect Scale (Watson & Clark, 1991)among others. No other adjunctive agents will be allowed during the eight weeks of the study. Patients will be seen for four weeks on a weekly basis, then biweekly thereafter.

Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit.

Depressed participants will also undergo functional MRI and neuropsychological testing twice, once at baseline and once after completion of the medication. 20 healthy control subjects with no history of Axis I disorders and who score less than 5 on the HDRS will participate in the baseline MRI, neuropsychological testing, and clinical ratings/questionnaires.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Imaging the Nucleus Accumbens in Major Depressed Patients 'Treated With Pramipexole
• Study Start Date: Feb 1, 2010
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pramipexole Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit.	Drug: Pramipexole; Patients will received increasing dose of pramipexole
No Intervention: Healthy Controls Non depressed, non-intervention comparison group

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Discontinued Study Due to Side-effects of the Medication [throughout the 8 weeks]

2. % Change in Hamilton Depression Rating Scale From Baseline to week8 [Baseline and weeks 8]

   Utilized the Hamilton Depression Rating Scale, 21-item version to assess depressive symptoms, with a range of 0-63. Higher scores equals more depression. For the change score, where higher equals greater improvement in depressive symptoms. Healthy controls were not utilized in this analysis, as no week 8 ratings for health controls were obtained.

3. Change in Mesolimbic Reward System Activity From Pre to Post Treatment (8 Weeks) [baseline and Week 8]

   Because of the limited number of depressed patients who completed the study (n=5) and noisy/unusable imaging data at various time points, this data was unable to be examined.

Secondary Outcome Measures

1. Mesolimibic Reward Activity Baseline Differences in Depression vs Healthy Controls [Baseline]

   Because of the small number of depressed patients and noisy/unusable data, analyses were not run.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Must meet DSM-IV criteria for Major Depressive Disorder

2. HAM-D score >18 on a 21-item assessment at eligibility

3. On at least an adequate dose of fluoxetine (40 mg/day), paroxetine (40 mg/day) paroxetine CR (50mg), sertraline (150 mg/day), citalopram (40 mg/day), escitalopram (20 mg/day), venlafaxine (150 mg/day), mirtazapine (30 mg/day), or duloxetine (60 mg/day) for at least 6 weeks (monotherapy).

4. 20-55 years of age

Exclusion Criteria:

1. Substance abuse in the past 6 months

2. ECT in the past 6 months

3. On a MAOI, tricyclic antidepressant, lithium, an antipsychotic, thyroid augmentation, 2 antidepressants simultaneously or lamotrigine

4. History of any psychosis including psychotic depression

5. History of Bipolar I, Bipolar II, or Bipolar NOS illness, or concurrent symptoms of mania or hypomania that do not meet the criteria for any bipolar disorder

6. History of compulsive gambling

7. Pregnant females or females of childbearing years not using adequate birth control in the opinion of the investigators

8. Known sensitivity to Pramipexole

9. Significant suicide risk in the opinion of the investigators

10. Significant medical conditions that would preclude safe participation in the study in the opinion of the investigators

11. Psychoactive drugs other than one of the antidepressants listed on Inclusion criteria #4. (A non-barbiturate sedative or hypnotic or benzodiazepine such as trazodone 50mg/day, zolpidem 10mg/day, lorazepam 3mg/day or clonazepam 2mg/day will be allowed if it has been in use for at least 1 month prior to the baseline visit.)

12. Significant abnormalities are observed in screening laboratory evaluation.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• National Alliance for Research on Schizophrenia and Depression

Investigators

• Principal Investigator: Jennifer Keller, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jennifer Keller, Principle Investigator, Stanford University
• ClinicalTrials.gov Identifier: NCT01066897
• Other Study ID Numbers: SU-02042010-4902; 17847
• First Posted: Feb 10, 2010
• Last Update Posted: May 16, 2017
• Last Verified: Apr 1, 2017

• Additional relevant MeSH terms: Depression; Pramipexole

Study Results

Participant Flow

Arm/Group Title	Pramipexole	Healthy Controls
Arm/Group Description	Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit. Pramipexole: Patients will received increasing dose of pramipexole	Non depressed, non treatment comparison group
Period Title: Overall Study
STARTED	7	9
COMPLETED	5	9
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Pramipexole	Healthy Controls	Total
Arm/Group Description	Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit. Pramipexole: Patients will received increasing dose of pramipexole	Non depressed, non treatment comparison group from baseline	Total of all reporting groups
Overall Participants	7	9	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.00 (14.12)	34.78 (14.0)	38.81 (14.41)
Sex: Female, Male (Count of Participants)
Female	7 100%	3 33.3%	10 62.5%
Male	0 0%	6 66.7%	6 37.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 11.1%	1 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	3 33.3%	3 18.8%
White	7 100%	5 55.6%	12 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%	9 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Discontinued Study Due to Side-effects of the Medication
Time Frame	throughout the 8 weeks

Outcome Measure Data

Analysis Population Description

# of participants who dropped out due to medication side-effects

Arm/Group Title	Pramipexole	Healthy Controls Who Did Not Take Medication
Arm/Group Description	Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit. Pramipexole: Patients will received increasing dose of pramipexole
Measure Participants	7	9
Count of Participants [Participants]	2 28.6%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole, Healthy Controls Who Did Not Take Medication
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.002
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	% Change in Hamilton Depression Rating Scale From Baseline to week8
Description	Utilized the Hamilton Depression Rating Scale, 21-item version to assess depressive symptoms, with a range of 0-63. Higher scores equals more depression. For the change score, where higher equals greater improvement in depressive symptoms. Healthy controls were not utilized in this analysis, as no week 8 ratings for health controls were obtained.
Time Frame	Baseline and weeks 8

Outcome Measure Data

Analysis Population Description

For two drop outs, used LOCF

Arm/Group Title	Pramipexole
Arm/Group Description	Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit. Pramipexole: Patients will received increasing dose of pramipexole
Measure Participants	7
Mean (Standard Deviation) [percentage reduction in depression score]	.46 (.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pramipexole
	Comments	For the 2 dropouts, used LOCF.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.067
	Comments
	Method	t-test, 2 sided
	Comments	One sample t-test to determine if the % change in HAMD was different from 0
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	.368
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: .44
	Estimation Comments

3. Primary Outcome

Title	Change in Mesolimbic Reward System Activity From Pre to Post Treatment (8 Weeks)
Description	Because of the limited number of depressed patients who completed the study (n=5) and noisy/unusable imaging data at various time points, this data was unable to be examined.
Time Frame	baseline and Week 8

Outcome Measure Data

Analysis Population Description

Because of the limited number of depressed patients who completed the study (n=5) and noisy/unusable imaging data at various time points, this data was unable to be examined.

Arm/Group Title	Pramipexole	Healthy Controls
Arm/Group Description	Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit. Pramipexole: Patients will received increasing dose of pramipexole	Non depressed, non-intervention comparison group
Measure Participants	0	0

4. Secondary Outcome

Title	Mesolimibic Reward Activity Baseline Differences in Depression vs Healthy Controls
Description	Because of the small number of depressed patients and noisy/unusable data, analyses were not run.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Because of the small number of depressed patients and noisy/unusable data, analyses were not run.

Arm/Group Title	Pramipexole	Healthy Controls
Arm/Group Description	Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit. Pramipexole: Patients will received increasing dose of pramipexole	Non depressed, non treatment comparison group
Measure Participants	0	0

Adverse Events

Time Frame	From date of randomization, every two weeks, assessed up to 8 weeks. Adverse events were only collected for the pramipexole group.
Arm/Group Title	Pramipexole
Arm/Group Description	Patients will receive 0.125 mg of pramipexole three times a day for the first week, 0.25 mg three times a day for the second week, and 0.5 mg three times a day for the third week. The dose will then be adjusted as needed by the treating physician (Dr. DeBattista), with a target range of 1.0 mg to 1.5 mg per day. Dose escalations will continue until 1) achievement of the primary endpoint (> 50% reduction from baseline on the HDRS scores; 2) intolerable side effects; or 3) completion of the 8-week study. Participants will be seen weekly the first four weeks and biweekly thereafter. Side effects, depression, and anhedonia will assessed at each visit. Pramipexole: Patients will received increasing dose of pramipexole
All Cause Mortality
	Pramipexole
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pramipexole
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Pramipexole
	Affected / at Risk (%)	# Events
Total	2/7 (28.6%)
Nervous system disorders
somnolence	1/7 (14.3%)	2
nausea	1/7 (14.3%)	1
restless leg	1/7 (14.3%)	1
insomnia	1/7 (14.3%)	1
Psychiatric disorders
odd thoughts	1/7 (14.3%)	1

Limitations/Caveats

The sample size is really too small for statistical analyses. Lack of funding prevented further recruitment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.