Imaging Dopamine Release in Depression

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02033369
• Collaborator: Columbia University (Other), Research Foundation for Mental Hygiene, Inc. (Other), Mclean Hospital (Other), Icahn School of Medicine at Mount Sinai (Other), National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 52
• Location: 1
• Arms: 2
• Actual Duration (Months): 40.9
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This study aims to determine whether ventral striatal dopamine release is a mechanism of reward motivation in major depression, whether dopamine release is low in depression, and whether DA release and reward motivation predict response to dopamine-targeted treatment with pramipexole.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Pramipexole	Phase 4

Detailed Description

Better understanding of the basic neurobiology of mood dysfunction appears necessary to enable further progress in the treatment of depression. Reward motivation (and the closely related construct of "reward learning") is a core neurobehavioral domain.(1,2) In major depressive disorder (MDD), low reward motivation is a key aspect of anhedonia, a cardinal symptom of MDD, and is related to resistance to treatment.(2,3) Although much has been learned about reward motivation's neurobiology and relevance to psychopathology, important gaps in our knowledge have impeded the application of basic science findings to improving treatment of MDD. Reward motivation in healthy subjects involves ventrostriatal (VST) dopamine (DA)(4,5), and reduced reward motivation is linked to MDD and anhedonia.(3,6) These data suggest that VST DA dysfunction might be present in MDD and manifested clinically by anhedonia. While DA neuroreceptor imaging studies have failed to verify this, they have been methodologically compromised. Limitations include imaging methods with poor resolution of functional striatal subregions, MDD samples heterogeneous for antidepressant use, and use of self-report measures of anhedonia, rather than objective behavioral testing of the specific domain of reward motivation. This will be the first study of both VST DA release (by PET imaging) and reward motivation, and will include patients with MDD and healthy volunteers. Reward motivation will be captured and operationalized as reward learning in a probabilistic reward task (prior to imaging). This will clarify if VST DA dysfunction is linked to impaired motivation in MDD. To test clinical implications in MDD patients, we will assess the relationship of VST DA release, reward motivation, and anhedonia to outcome of subsequent open label treatment with the DA D2 receptor agonist pramipexole.

Study Design

• Study Type: Interventional
• Actual Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Ventrostriatal Dopamine Release and Reward Motivation in MDD
• Actual Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pramipexole Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg.	Drug: Pramipexole; Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day.; Other Names: Mirapex (brand name)
No Intervention: Healthy Control Healthy volunteers were matched to MDD group subjects by age, gender, and ethnicity, and will have no lifetime psychiatric disorders.

Outcome Measures

Primary Outcome Measures

1. Change in Hamilton Rating Scale for Depression [Baseline and 6 weeks]

   Hamilton Rating Scale for Depression (HRSD), 17-item version. This standard scale will be used to assess severity of depression, looking at change in total score from baseline to week 6, rating severity of depression on a scale from 0 (least depression) to 50 (greatest depression)

Secondary Outcome Measures

1. Change in Snaith Hamilton Pleasure Scale [Baseline and 6 weeks]

   Fourteen-item self-rated anhedonia scale. Items were comprised of statements that participants rated as "strongly disagree" (1), "disagree" (2), "agree" (3), or "strongly agree" (4). The lowest possible score was 14, the highest possible score was 56.

2. Change in Temporal Experience of Pleasure Scale - Anticipatory Subscale [Baseline and 6 weeks]

   A validated self-rated scale shown to assess anticipatory pleasure. It will be used for exploratory analyses of anhedonia. 18 items were measured on a scale of 1 (very false for me) to 6 (very true for me). Higher scores indicate higher pleasure. Item scores were added for a lowest possible score of 18 and highest possible score of 108.

3. Change in Mood and Anxiety Symptom Questionnaire, Short Form [Baseline and 6 weeks]

   Change in Mood and Anxiety Symptom Questionnaire, Short Form. A 62-item scale assessing anxiety and depression. Items were measured on a scale of 1-5, higher number indicating higher levels of symptoms.The lowest possible score was 62, and the highest 310.

4. Change in the Apathy Evaluation Rating Scale [Baseline and 6 weeks]

   A validated self-rated 18 item scale assessing apathy. Items were rated from 1 (not at all true) to 4 (very true). Higher scores indicate lower apathy, lower scores indicate higher apathy. Lowest possible score is 18, highest possible score is 72.

5. Change in Clinical Global Improvement - Severity Scale [6 weeks]

   Seven-point Likert scale rating clinical severity of mental illness from 1 (least severe) to 7 ( most severe). Physician-rated scale. One item.

6. Change in Temporal Experiences of Pleasure Scale -- Consummatory Subscale [Baseline and 6 weeks]

   A validated self-rated scale shown to assess consummatory pleasure. It will be used for exploratory analyses of anhedonia. 18 items were measured on a scale of 1 (very false for me) to 6 (very true for me). Higher scores indicate higher pleasure. Item scores were added for a lowest possible score of 18 and highest possible score of 108.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Weight between 44 kg and 115 kg

• Meets DSM-IV criteria for principal diagnosis of MDD, current major depressive episode, without psychotic features

• Score of >16 and <29 on 17-item Hamilton Rating Scale for Depression

• Psychotropic-naïve, as defined by lifetime <2 weeks treatment with antidepressants, anxiolytics or antipsychotics

• Able to tolerate a treatment-free period during study participation

• Able to provide informed consent

Exclusion Criteria:

• A principal diagnosis of any current Axis I psychiatric disorder other than the MDD

• Lifetime diagnosis of any psychotic disorder, bipolar disorder, mental retardation, attention deficit/hyperactivity disorder, or substance use disorders (including nicotine use disorders)

• Serious suicidal risk or history of violent behavior which would make participation in the protocol unsafe

• Any tobacco use in the prior three months (if not already excluded for abuse/dependence by #1)

• Illicit drug use in the prior three months, as evidenced by history or urine toxicology screen

• Women who are pregnant, nursing, postmenopausal, or using hormonal methods of birth control

• Women who are not using an effective birth control method or sexual abstinence during the ten days before the scan

• Any medical or neurological problem that might affect interpretation of findings or safety of participation (e.g., blood dyscrasias, lymphomas, hypersplenism, endocrinopathies, renal failure or chronic obstructive lung disease, malignancy, neurological diseases of the brain, history of seizures or head trauma), low hemoglobin (Hb < 12 gm/dL in males, Hb < 10.5 gm/dL in females))

• Blood donation within 4 weeks of study

• Metal implants or paramagnetic objects in the body that might affect safety of undergoing MRI (e.g., heart pacemaker, shrapnel, bullets, surgical prostheses or surgical clips), as determined in consultation with a neuroradiologist and according to the guidelines set forth in the reference: "Guide to MR procedures and metallic objects" Shellock; Lippincott Williams and Wilkins, NY, 2001

• More than one major risk factor for coronary artery disease (e.g. hyperlipidemia, sedentary lifestyle). Smokers are already excluded by #4 above, and diabetics by #8 above

• Systolic blood pressure > 140 or diastolic blood pressure > 90 based on at least two readings at rest

• History of untoward reaction to amphetamine or other stimulant medication, or pramipexole

• Any psychotropic treatment in the past 3 weeks (or depot medication in the past 6 months), except for lorazepam,which may be administered as needed prior to imaging day

• Current, past or anticipated exposure to radiation in the workplace, or participation in nuclear medicine procedures, including research protocols (In case of previous exposure to activity due to research studies, subjects will be eligible if all conditions listed below are fulfilled: 1) The injected dose and dosimetry of the radiotracer are known; 2) Except for research studies, the subject has not been exposed to radiation (workplace and medical); 3) Adding prior exposure to the exposure due to the study will result in a yearly cumulative exposure lower than the FDA limit for research studies

• Family history of schizophrenia in parents, siblings, or children

• Ongoing cognitive-behavioral or interpersonal psychotherapy for depression (Supportive therapy is not an exclusion)

• Ongoing treatment with cimetidine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• Columbia University
• Research Foundation for Mental Hygiene, Inc.
• Mclean Hospital
• Icahn School of Medicine at Mount Sinai
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Franklin Schneier, MD, NYSPI

Study Documents (Full-Text)

None provided.

More Information

Publications

• Forbes EE, Hariri AR, Martin SL, Silk JS, Moyles DL, Fisher PM, Brown SM, Ryan ND, Birmaher B, Axelson DA, Dahl RE. Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. Am J Psychiatry. 2009 Jan;166(1):64-73. doi: 10.1176/appi.ajp.2008.07081336. Epub 2008 Dec 1.
• Kumar P, Waiter G, Ahearn T, Milders M, Reid I, Steele JD. Abnormal temporal difference reward-learning signals in major depression. Brain. 2008 Aug;131(Pt 8):2084-93. doi: 10.1093/brain/awn136. Epub 2008 Jun 25.
• Pizzagalli DA, Iosifescu D, Hallett LA, Ratner KG, Fava M. Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task. J Psychiatr Res. 2008 Nov;43(1):76-87. doi: 10.1016/j.jpsychires.2008.03.001. Epub 2008 Apr 22.
• Sanislow CA, Pine DS, Quinn KJ, Kozak MJ, Garvey MA, Heinssen RK, Wang PS, Cuthbert BN. Developing constructs for psychopathology research: research domain criteria. J Abnorm Psychol. 2010 Nov;119(4):631-9. doi: 10.1037/a0020909.
• Treadway MT, Zald DH. Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev. 2011 Jan;35(3):537-55. doi: 10.1016/j.neubiorev.2010.06.006. Epub 2010 Jul 11. Review.
• Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, Schmidt M, Claes S. Reduced reward learning predicts outcome in major depressive disorder. Biol Psychiatry. 2013 Apr 1;73(7):639-45. doi: 10.1016/j.biopsych.2012.10.014. Epub 2012 Dec 8.

• Responsible Party: Franklin Schneier, Professor, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT02033369
• Other Study ID Numbers: #6853; 1R01MH099322-01A1
• First Posted: Jan 10, 2014
• Last Update Posted: Nov 1, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Franklin Schneier, Professor, New York State Psychiatric Institute: Major depressive disorder; MDD; depression; pramipexole
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Pramipexole

Study Results

Participant Flow

Arm/Group Title	MDD Patients	Healthy Controls
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day	Individuals without depression
Period Title: Overall Study
STARTED	26	26
COMPLETED	21	21
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	MDD Patients	Healthy Control Patients	Total
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day	Healthy control patients did not receive study medication and only have baseline measures.	Total of all reporting groups
Overall Participants	26	25	51
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.5 (6.1)	26.5 (5.6)	26.5 (5.8)
Sex: Female, Male (Count of Participants)
Female	13 50%	12 48%	25 49%
Male	13 50%	13 52%	26 51%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 38.5%	9 36%	19 37.3%
Not Hispanic or Latino	16 61.5%	16 64%	32 62.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 11.5%	3 12%	6 11.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 19.2%	5 20%	10 19.6%
White	12 46.2%	10 40%	22 43.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 23.1%	7 28%	13 25.5%
Hamilton Rating Scale for Depression (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	20.3 (2.7)	0.2 (0.4)	10.4 (10.3)
Snaith Hamilton Pleasure Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	31.9 (6.5)	18.9 (4.8)	25.7 (8.7)
Temporal Experience of Pleasure Scale - Anticipatory Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	36.1 (8.0)	49.0 (5.2)	42.4 (9.3)
Mood and Anxiety Symptom Questionnaire (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	174.5 (28.6)	83.9 (13.3)	130.1 (50.8)
Apathy Evaluation Rating Scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	41.8 (9.7)	23.8 (4.9)	33.0 (11.8)
Clinical Global Impression Severity (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.9 (0.7)	1.0 (0)	1.9 (0.4)
Temporal Experience of Pleasure Scale - Consummatory Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	29.9 (7.6)	38.4 (7.2)	34.1 (8.5)

Outcome Measures

1. Primary Outcome

Title	Change in Hamilton Rating Scale for Depression
Description	Hamilton Rating Scale for Depression (HRSD), 17-item version. This standard scale will be used to assess severity of depression, looking at change in total score from baseline to week 6, rating severity of depression on a scale from 0 (least depression) to 50 (greatest depression)
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Healthy control subjects were not assessed for outcome measures because by study design they received no therapeutic intervention.

Arm/Group Title	Pramipexole
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day
Measure Participants	22
Mean (Standard Deviation) [units on a scale]	8.4 (5.4)

2. Secondary Outcome

Title	Change in Snaith Hamilton Pleasure Scale
Description	Fourteen-item self-rated anhedonia scale. Items were comprised of statements that participants rated as "strongly disagree" (1), "disagree" (2), "agree" (3), or "strongly agree" (4). The lowest possible score was 14, the highest possible score was 56.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Healthy control subjects were not assessed for outcome measures because by study design they received no therapeutic intervention.

Arm/Group Title	Pramipexole
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day
Measure Participants	22
Mean (Standard Deviation) [units on a scale]	26 (7.51)

3. Secondary Outcome

Title	Change in Temporal Experience of Pleasure Scale - Anticipatory Subscale
Description	A validated self-rated scale shown to assess anticipatory pleasure. It will be used for exploratory analyses of anhedonia. 18 items were measured on a scale of 1 (very false for me) to 6 (very true for me). Higher scores indicate higher pleasure. Item scores were added for a lowest possible score of 18 and highest possible score of 108.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Healthy control subjects were not assessed for outcome measures because by study design they received no therapeutic intervention.

Arm/Group Title	Pramipexole
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day
Measure Participants	22
Mean (Standard Deviation) [units on a scale]	43.2 (7.9)

4. Secondary Outcome

Title	Change in Mood and Anxiety Symptom Questionnaire, Short Form
Description	Change in Mood and Anxiety Symptom Questionnaire, Short Form. A 62-item scale assessing anxiety and depression. Items were measured on a scale of 1-5, higher number indicating higher levels of symptoms.The lowest possible score was 62, and the highest 310.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Healthy control subjects were not assessed for outcome measures because by study design they received no therapeutic intervention.

Arm/Group Title	Pramipexole
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day
Measure Participants	22
Mean (Standard Deviation) [units on a scale]	123.1 (36.3)

5. Secondary Outcome

Title	Change in the Apathy Evaluation Rating Scale
Description	A validated self-rated 18 item scale assessing apathy. Items were rated from 1 (not at all true) to 4 (very true). Higher scores indicate lower apathy, lower scores indicate higher apathy. Lowest possible score is 18, highest possible score is 72.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Healthy control subjects were not assessed for outcome measures because by study design they received no therapeutic intervention.

Arm/Group Title	Pramipexole
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day
Measure Participants	22
Mean (Standard Deviation) [units on a scale]	31.7 (9.5)

6. Secondary Outcome

Title	Change in Clinical Global Improvement - Severity Scale
Description	Seven-point Likert scale rating clinical severity of mental illness from 1 (least severe) to 7 ( most severe). Physician-rated scale. One item.
Time Frame	6 weeks

Outcome Measure Data

Analysis Population Description

Healthy control subjects were not assessed for outcome measures because by study design they received no therapeutic intervention.

Arm/Group Title	Pramipexole
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day
Measure Participants	22
Mean (Standard Deviation) [units on a scale]	2.59 (1.10)

7. Secondary Outcome

Title	Change in Temporal Experiences of Pleasure Scale -- Consummatory Subscale
Description	A validated self-rated scale shown to assess consummatory pleasure. It will be used for exploratory analyses of anhedonia. 18 items were measured on a scale of 1 (very false for me) to 6 (very true for me). Higher scores indicate higher pleasure. Item scores were added for a lowest possible score of 18 and highest possible score of 108.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Healthy control subjects were not assessed for outcome measures because by study design they received no therapeutic intervention.

Arm/Group Title	Pramipexole
Arm/Group Description	Six weeks of treatment with oral pramipexole, initiated at 0.25 mg/day and titrated to a maximum daily dose of 2.5 mg. Pramipexole: Dose will be started at 0.125 mg bid, and increased by 0.25 mg/day every 3-4 days to a target range of 1.0 - 2.5 mg/day
Measure Participants	22
Mean (Standard Deviation) [units on a scale]	35.6 (6.6)

Adverse Events

Time Frame	6 weeks
Adverse Event Reporting Description	Information was collected on a side effect checklist, with each adverse event rated from 0 (absent) to 3 (severe). A subject was considered to have experienced a side effect during the study if the rating for that adverse event increased in severity at any point during the treatment. Adverse events were not assessed for Healthy Controls, because by study design they did not receive any therapeutic intervention.
Arm/Group Title	MDD Patients
Arm/Group Description	Only patients with MDD received treatment. There was only one arm.
All Cause Mortality
	MDD Patients
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Serious Adverse Events
	MDD Patients
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Other (Not Including Serious) Adverse Events
	MDD Patients
	Affected / at Risk (%)	# Events
Total	22/22 (100%)
Blood and lymphatic system disorders
Bruising	2/22 (9.1%)	2
Eye disorders
Blurry Vision	6/22 (27.3%)	6
Gastrointestinal disorders
nausea	18/22 (81.8%)	18
Heartburn	7/22 (31.8%)	7
Vomiting	7/22 (31.8%)	7
Decreased Appetite	6/22 (27.3%)	6
Increased Appetite	6/22 (27.3%)	6
Constipation	4/22 (18.2%)	4
Diarrhea	5/22 (22.7%)	5
General disorders
Dry Mouth	10/22 (45.5%)	10
fatigue	2/22 (9.1%)	2
Musculoskeletal and connective tissue disorders
tremor	2/22 (9.1%)	2
Impaired Coordination	4/22 (18.2%)	4
Nervous system disorders
headache	13/22 (59.1%)	13
Lightheadedness	10/22 (45.5%)	10
Dizziness	8/22 (36.4%)	8
Psychiatric disorders
Restlessness	9/22 (40.9%)	9
Insomnia	9/22 (40.9%)	9
somnolence	11/22 (50%)	11
Sleep Attacks	5/22 (22.7%)	5
Forgetfulness	7/22 (31.8%)	7
Impaired Concentration	2/22 (9.1%)	2
compulsive behaviorws	3/22 (13.6%)	3
Reproductive system and breast disorders
decreased libido	7/22 (31.8%)	7
Sexual Dysfunction	3/22 (13.6%)	3
Skin and subcutaneous tissue disorders
Sweating	4/22 (18.2%)	4
Skin Problems	5/22 (22.7%)	5

Limitations/Caveats

[Not Specified]

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.