Dallas 2K: A Natural History Study of Depression (D2K)

• ClinicalTrials.gov Identifier: NCT02919280
• Recruitment Status: Recruiting
• First Posted: September 29, 2016
• Last Update Posted: May 31, 2022
• Sponsor: University of Texas Southwestern Medical Center
• Collaborator: The Hersh Foundation
• Information provided by (Responsible Party): Madhukar H. Trivedi, MD, University of Texas Southwestern Medical Center

Study Description

Brief Summary:

The Dallas 2K is a 10-year natural history, longitudinal, prospective study of a cohort of 2,000 participants that will help uncover the socio-demographic, lifestyle, clinical, psychological and neurobiological factors that contribute to anti-depressant treatment response: remission, recurrence, relapse and individual outcomes in depressive disorders. Hence, the expected duration of this study is 20 years in length. Since this is an observational study, investigators will explore a comprehensive panel of carefully selected participant specific parameters: socio-demographic (age, ethnicity, economic); lifestyle (physical activity, substance use); clinical (medical history, anxious depression, early life trauma), biological (biomarkers in blood, saliva, urine), behavioral (cognitive, emotional), neurophysiological (EEG), and neuroimaging (structural, functional brain circuitry) with the goal to develop the most robust predictive models of treatment response and of depression outcomes. There is no medication or non-medication treatment or intervention provided by this study.

Subjects will have elevated symptomatology of nonpsychotic chronic or recurrent depressive disorder and will be currently receiving or will be prescribed standard of care medication or non-medication based treatments by their providers/clinicians. The study cohort will reflect the wide range of patients seen in typical primary or psychiatric care settings, and may include unipolar or bipolar disorders and dysthymia (a more chronic form of depression). The cohort will be broadly representative of and generalizable to the US general population as a whole.

Condition or disease	Intervention/treatment
Depression; Depression, Bipolar	Other: Observational Study

Detailed Description:

This is a non-randomized, natural history, non-treatment, longitudinal cohort study. Participants will be receiving standard of care treatment for depression and other comorbidities from their treating clinician and will be allowed to continue such treatments in this study. There are no experimental study procedures, other than methods used for data capture (questionnaires, blood collection, EEG and MRI). Participants will be expected to visit study site (s) for repeated collection of data (assessments, biospecimens, and imaging procedures), up to 4 times a year for 10 years. A reduced battery of tests is allowable if subject is not able or willing to complete the full battery after the baseline visit.

2000 research participants will be enrolled and followed over an eight-year period (each participant will be followed for 10-years) with collection of clinical and depression measurement assessments, measurement of vital signs, collection of biospecimens for biochemical and genetic analyses, electroencephalogram (EEG) with behavioral assessments, and neuroimaging using magnetic resonance imaging (MRI). Skin punch biopsy will be performed in a sub-set of the research cohort, defined as demonstrating a heritable phenotype of depression. Stool sample will be performed in a sub-set of the research cohort, defined as demonstrating a heritable phenotype of depression.

Participants will complete PHQ-9 (Patient Health Questionnaire-9), a brief self-administered measure of depression severity, and PS (Psychosis Screening) questionnaire, as part of inclusion and exclusion criteria, respectively. Participants will then complete all required computer-assisted self-rating and clinician-administered instruments. The self-rating instruments are expected to take approximately 2.5 hours using an iPad or laptop computer, and will collect detailed socio-demographic, life habits, family and medical history, and depression severity and treatment history. After completing the questionnaires, the research personnel will measure the subject's blood pressure, height, waist and hip circumference and weight. The subject will then provide blood, saliva and urine samples (morning blood draw appointments will be offered whenever participants agree to fast before blood draws but non-fasting blood will also be collected, when not possible to obtain fasting blood).

For study assessments, specimen collection; and EEG and behavioral phenotyping, Dallas 2K study participants will require a 6-hour study visit to UT Southwestern. Participants will be given the option to split their visit into two if that is more convenient, and visit 2 will be used to perform EEG and behavioral assessments. Participants choosing the initial visit at an MDN clinician's office will complete screening, assessments and biospecimen collection at the MDN office but may require a 3-hour visit to UT Southwestern clinics for EEG and behavioral assessments. The MRI may be performed during a separate 2-hour visit to UT Southwestern MRI facility.

Schedule of study visits, procedures and duration:

Study A - Assessments and Questionnaires, 3 hours; Study B - EEG and Behavioral Phenotyping, 3 hours; Study C - Neuroimaging (MRI), 2 hours; Study D - Sub-Study only: Skin punch biopsy, 30 minutes; Study E - Sub-Study only: Stool Sample, 15 minutes; Study F - Sub-Study only: mHealth, Continuous monitoring via a wristband (i.e. fitbit) and/or mhealth application downloaded on a Android operating smartphone.

Studies A and B can be combined into a single 6-hour visit when occurring at UT Southwestern.

EEG and behavioral phenotyping and Neuroimaging will be performed at 3-month intervals.

For participants in the optional sub-study, skin punch biopsy, Study D will be performed during any one of the other visits, depending on participants' convenience.

For participants in the optional sub-study stool sample, study E will be performed up to 4 visits per year for 10-years.

For participants in the optional sub-study mhealth study, Study F will be a continuous monitoring of your physical activity, sleep patterns etc. via a wristband (i.e. Fitbit) and/or mHealth application downloaded onto an Android operating Smartphone.

In addition, monthly remote assessments are completed between onsite visits starting from the baseline visit.

Study A will then be repeated at 3-month intervals for up to 4 times a year, during follow-up study visits.

Phlebotomy Procedures Blood samples will be collected from participants by trained phlebotomists, who will draw the sample using standard venipuncture procedures, through a single venipuncture using a small gauge needle. Universal precautions will be observed by the phlebotomists during all draws. The sample collection tubes, priority and volume collected are indicated in the protocol. Each tube will be labeled and packaged for processing and storage.

Electrophysiology (EEG) Procedures: Participants will undergo electrophysiology measures at baseline and at 3-month intervals. Procedures for each of these measures are outlined below. Detailed EEG procedures will be described in the EEG and Behavioral Tasks Procedures Manual, respectively. The EEG markers in this study can be divided into three groups. Participants will first undergo resting EEG. Resting EEG is measured during four, 2 minute periods, half the time with the participants' eyes open, and the other half with the participants' eyes closed. The second EEG measure will specifically localize theta activity using a technique called Low Resolution Electromagnetic Tomography (LORETA). Finally, participants will have head-phones placed, and will be presented with 1000 Hz tones at 5 different intensity levels. The loudness dependency of auditory evoked potential (LDAEP) will be measured during this time. The total time estimate for completion of the EEG collection at each visit is approximately 2 hours. The EEG workgroup will ensure that adequate training, standardization of measures, and validation of equipment is maintained for data consistencies and quality control purposes.

Behavioral Phenotyping: The investigators will administer five distinct tasks to participants, to assess four domains: 1) psychomotor slowing, 2) cognitive control, 3) working memory, and 4) reward responsiveness. To assess these domains, the investigators plan to administer the following tasks: psychomotor slowing, Choice RT task (~5 min) and word fluency task (~5 min); cognitive control, the Flanker task (~10 min); working memory, the A not B task (~10 min); and reward responsiveness, the Probabilistic Reward task (~10 min). This task measures the subject's ability to modify behavior in response to rewards. On each trial, the subject sees a cartoon face with a short or long mouth. The task is to indicate whether a short or long mouth was presented by pressing one of two buttons. Critically, the size difference between the short and long mouths is very small, and correct responses of one type (e.g., short mouth) are followed by monetary rewards three times more frequently than correct responses of the other type (e.g., long mouth). The primary dependent measure is response bias: the degree to which the subject preferentially chooses the response that is more frequently rewarded (in this example, short mouth vs. long mouth). Other dependent measures include RT and a measure of the subject's ability to discriminate between the mouth sizes (28). All tasks will be presented using Eprime software, under standardized procedures across sites. The Behavioral Phenotyping workgroup will ensure that quality control is maintained and that adequate training and standardization of measures is obtained prior to study related activities commencing. The total time the investigators estimate for completion of behavioral tasks at each study visit is about 1 hour.

Neuroimaging: Eligible participants will undergo neuroimaging at baseline and at 3-month intervals. Neuroimaging includes both functional MRI and structural acquisitions. A brief description of procedures for each of these is outlined below; detailed descriptions will be in the Neuroimaging Procedures Manual. In total, the investigators estimate that approximately 90 minutes will be spent in the scanner per visit. In addition, research personnel will spend about 30 minutes preparing participants. Neuroimaging will be performed at baseline (study entry) and at 3-month intervals, for a total of 10 total neuroimaging sessions for the study duration.

The collection of socio-demographics, lifestyle, clinical and other health-related information obtained through self-report questionnaires and clinician interviews will complement the physical, biological, neuroimaging (including EEG) measurements collected at study visits. The information obtained will form a database that allows a wide range of research questions, both anticipated and unforeseen, to be addressed in the future.

Some questionnaires will be given to participant parents as required for minors. Additional assessments completed with minors will be done with study staff to assist with any questions or difficulty with the assessments.

Note: The schedule of assessments to be completed will vary from time to time within this longitudinal study to help balance the data between age, gender and diagnosis breakdown of our enrolled participants for data analyses. The schedule of assessments will NOT exceed the following:

1. Monthly Surveys: 12 times a year
2. MRI: 4 times a year
3. EEG: 4 times a year
4. Biospecimen collection: 4 times a year
5. Cognitive Behavioral Tasks (e.g. NIH Toolbox / Cogstate / Emoticom)
6. Extensive Self-report and Clinician rated assessments: 4 times a year
7. Optional Stool Sample collection: 4 times a year
8. Optional Dermal Biopsy: 1 time only
9. Optional M-health: Duration of the study (starting from Baseline)

Study Design

• Study Type: Observational
• Estimated Enrollment: 2000 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Dallas 2K: A Natural History Study of Depression
• Study Start Date: September 2016
• Estimated Primary Completion Date: September 2026
• Estimated Study Completion Date: September 2026

Groups and Cohorts

Group/Cohort	Intervention/treatment
No treatment; This is an observational study. No intervention / treatment involved.	Other: Observational Study; The Dallas 2K is a 10-year natural history, longitudinal, prospective study of a cohort of 2,000 participants. There is no medication or non-medication treatment or intervention provided by this study.

Outcome Measures

Primary Outcome Measures :

1. Longitudinal changes in depression severity of subjects with elevated symptomatology on Patient Health Questionnaire (PHQ-9) for non-psychotic depressive disorders. [ Time Frame: 10 years ]

Secondary Outcome Measures :

1. Comparison of Longitudinal changes in functioning as measured by Magnetic Resonance imaging in patients with severe depression [ Time Frame: 10 years ]
2. Comparison of Longitudinal changes in functioning as measured by quantitative electroencephalography (EEG) in patients with severe depression. [ Time Frame: 10 years ]
3. Comparison of Longitudinal changes in fluid based biomarkers as measured by proteomic methods in patients with severe depression. [ Time Frame: 10 years ]
4. Comparison of Longitudinal changes in fluid based biomarkers as measured by metabolomics methods in patients with severe depression. [ Time Frame: 10 years ]
5. Comparison of Longitudinal changes in fluid based biomarkers as measured by transcriptomic methods in patients with severe depression. [ Time Frame: 10 years ]
6. Comparison of Longitudinal changes in fluid based biomarkers as measured by genomic methods in patients with severe depression. [ Time Frame: 10 years ]
7. Comparison of Longitudinal changes in fluid based biomarkers as measured by epigenomic methods in patients with severe depression. [ Time Frame: 10 years ]

Biospecimen Retention:   Samples With DNA

One of the aims of this study is to establish a Dallas 2K biospecimen resource consisting of blood, plasma, serum, PBMCs, DNA, RNA, saliva and urine samples collected from subjects at baseline and at follow-up visits, as a platform for translational research into biochemical and molecular characterization of depression.

Eligibility Criteria

• Ages Eligible for Study: 10 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

The following group is being targeted for this observational study:

1. Depressed patients
2. Lifetime or Current Diagnosis of a Mood Disorder
3. Bipolar Disorder
4. Health Controls with NO Psychiatric Diagnosis ( For Comparison Purposes)

Criteria

Criteria for Inclusion of participants:

A potential participant will be eligible for participation in this study if the following criteria are met:

1. Male and female adult or youth aged 10 and older of any race or ethnicity.
2. Ability to speak, read, and understand English. However, the parent(s) or legal guardians of minors may either speak English or Spanish as the consenting process can be conducted bilingually.
3. A lifetime or a current diagnosis of a mood disorder based upon a semi-structured diagnostic interview.
4. Adults age 18 and older must be able to provide written informed consent; for youth younger than age 18, a parent or legal guardian must provide written informed consent, and the child or teen must provide written informed assent.

Eligibility for Healthy Controls

For comparison purposes, potential health control participants who do NOT have a psychiatric diagnosis will be enrolled as part of the healthy control arm of this study.

1. Male and female adult or youth aged 10 and older of any race or ethnicity.
2. Ability to speak, read, and understand English. However, the parent(s) or legal guardians of minors may either speak English or Spanish as the consenting process can be conducted bilingually.
3. Adults age 18 and older must be able to provide written informed consent; for youth younger than age 18, a parent or legal guardian must provide written informed consent, and the child or teen must provide written informed assent.

Criteria for Exclusion of Participants

A potential participant will NOT be eligible for participation in this study if any of the following criteria are met:

1. History of schizophrenia, schizoaffective disorders or chronic psychotic disorders based upon a semi-structured diagnostic interview.
2. Diagnosis of human immunodeficiency virus (HIV) or hepatitis B or C (human immunodeficiency virus (HIV) testing is not required for this study).
3. Unable to provide a stable home address and contact information.
4. Has any condition for which, in the opinion of the investigator or designee, study participation would not be in their best interest (including but not limited to cognitive impairment, unstable general medical condition, intoxication, active psychosis) or that could prevent, limit, or confound the protocol-specified assessments.
5. Requires immediate hospitalization for psychiatric disorder or suicidal risk as assessed by a licensed study clinician.

Eligibility for Healthy Controls

A potential Healthy Control participant will NOT be eligible for participation in this study if any of the following criteria are met:

1. A lifetime or a current history of a mood disorder based upon a semi-structured diagnostic interview.
2. Meets any exclusion criteria as part of the main D2K study interview.

Contacts and Locations

Contacts

Contact: Ronnie Pedroncelli, BS; 214 648 4357; D2K@UTSouthwestern.edu

Contact: Sangita Sethuram, MBA; 214-648-4357; D2K@UTSouthwestern.edu

Locations

United States, Texas

University of Texas Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

Contact: Sangita Sethuram, MBA, CCRP 214-648-4357 D2K@UTSouthwestern.edu

Principal Investigator: Madhukar Trivedi, MD

Sponsors and Collaborators

University of Texas Southwestern Medical Center

The Hersh Foundation

Investigators

• Principal Investigator: Madhukar Trivedi, MD; University of Texas Southwestern Medical Center

More Information

Publications of Results:

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.

Trivedi MH, Greer TL, Grannemann BD, Church TS, Somoza E, Blair SN, Szapocznik J, Stoutenberg M, Rethorst C, Warden D, Ring KM, Walker R, Morris DW, Kosinski AS, Kyle T, Marcus B, Crowell B, Oden N, Nunes E. Stimulant reduction intervention using dosed exercise (STRIDE) - CTN 0037: study protocol for a randomized controlled trial. Trials. 2011 Sep 19;12:206. doi: 10.1186/1745-6215-12-206.

Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006 Jan;163(1):28-40. doi: 10.1176/appi.ajp.163.1.28.

Bloom BS. Prevalence and economic effects of depression. Manag Care. 2004 Jun;13(6 Suppl Depression):9-16.

Other Publications:

Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS; National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003 Jun 18;289(23):3095-105. doi: 10.1001/jama.289.23.3095.

• Responsible Party: Madhukar H. Trivedi, MD, Professor, University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT02919280
• Other Study ID Numbers: STU 112015-021
• First Posted: September 29, 2016
• Last Update Posted: May 31, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Depression; Depressive Disorder; Bipolar Disorder; Behavioral Symptoms; Mood Disorders; Mental Disorders; Bipolar and Related Disorders