Theophylline for Depression Study (T-DEP)

November 3, 2021 updated by: Hyong Jin Cho, University of California, Los Angeles

Pilot Randomized Controlled Trial of Theophylline for Attenuation of Lipopolysaccharide-Induced Depressive Symptoms

Depression is very common and poses a huge disease burden. About 20% of the US population suffers from depression at least once in their lifetime. Inflammations that are hidden inside our body as a result of aging, obesity, chronic diseases, or certain treatments (e.g., interferon for hepatitis C) appear to cause depressive symptoms and even clinical depression. Individuals with such inflammations are more likely to suffer from depression and are less likely to respond to currently available antidepressant medications. This study will test theophylline, a medication currently used for asthma treatment, as a new way to mitigate depressive symptoms in response to such inflammations. This study begins with a 90-minute screening session to determine whether participants are eligible to join the main study. Those who meet the eligibility criteria will then join the main study, which will consist of taking theophylline or methylcellulose (i.e., oral placebo) for 2 weeks at home and an 8-hour session at the UCLA Medical Center. Approximately 20 healthy adults will be recruited for participation in the study. During the course of the study, participants will take theophylline or methylcellulose for 2 weeks at home and then will be injected either lipopolysaccharide (LPS) or saline (i.e., intravenous placebo) at the UCLA Medical Center. LPS is a bacterial substance that can initiate chemical reactions that are similar to those seen in individuals with mild sickness symptoms, such as a slight increase in body temperature, muscle aches, or tiredness. It is a safe way of investigating the body's response to inflammation and how these changes may alter cognitive, emotional, or neural function. It has been given thousands of times to healthy volunteers - both younger and older adults - without any serious side effects.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Cousins Center for Psychoneuroimmunology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • in good general health (as evaluated during the phone and in-person screening sessions)
  • aged 18-65 years
  • if female, using adequate birth control

Exclusion Criteria:

  • history of hypersensitivity to xanthine derivatives (a contraindication to theophylline treatment)
  • pregnant or planning to become pregnant in the next 6 months
  • current breastfeeding
  • chronic diseases such as cardiovascular disease, hepatic impairment, peptic ulcer disease, and seizure disorders
  • current use of prescription medications such as steroids, non-steroid anti-inflammatory drugs, immune modifying drugs, opioid analgesics, and psychotropics
  • Axis I psychiatric disorders including current major depressive disorder
  • current depressive symptoms assessed by the Patient Health Questionnaire (PHQ-9 ≥ 5)
  • heavy smoking (1 pack or more per day)
  • excessive caffeine use (>600 mg/day)
  • Body-mass index > 35 due to the effects of obesity on cytokine activity
  • evidence of recreational drug use from urine test
  • evidence of pregnancy from urine test
  • evidence of clinically significant rhythm abnormality on a resting electrocardiogram (ECG)
  • clinically significant abnormalities on screening laboratory tests

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PO theophylline & IV LPS
Oral (PO) theophylline 400 mg/day for 2 weeks followed by a single intravenous (IV) bolus of lipopolysaccharide (LPS) 0.8 ng/kg of body weight
Drug: Theophylline ER
Capsules of theophylline ER
Biological: Lipopolysaccharide (LPS)
Purified bacterial wall component as an inflammatory challenge
Experimental: PO placebo & IV LPS
PO methylcellulose (placebo) daily for 2 weeks followed by a single intravenous (IV) bolus of lipopolysaccharide (LPS) 0.8 ng/kg of body weight
Biological: Lipopolysaccharide (LPS)
Purified bacterial wall component as an inflammatory challenge
Other: PO placebo
Capsules of methylcellulose
Experimental: PO theophylline & IV placebo
PO theophylline 400 mg/day for 2 weeks followed by a single IV bolus of 0.9% saline
Drug: Theophylline ER
Capsules of theophylline ER
Other: IV placebo
Normal (0.9%) saline
Placebo Comparator: PO placebo & IV placebo
PO methylcellulose (placebo) daily for 2 weeks followed by a single IV bolus of 0.9% saline
Other: PO placebo
Capsules of methylcellulose
Other: IV placebo
Normal (0.9%) saline

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in depressed mood from baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Short Form of the Profile of Mood States (POMS-SF) Depression Subscale with higher scores indicating more severe depressed mood (range 0-32)
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in tension/anxiety from baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Short Form of the Profile of Mood States (POMS-SF) Tension Subscale with higher scores indicating more severe tension/anxiety (range 0-24)
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Change in depressive symptoms from baseline
Time Frame: At baseline and then at 2, 4, and 6 hours after LPS (or saline) administration
Montgomery-Asberg Depression Rating Scale (MADRS): a clinician-rated questionnaire of depressive symptoms with scores ranging from 0 to 60, with higher scores indicating more severe depressive symptoms
At baseline and then at 2, 4, and 6 hours after LPS (or saline) administration
Change in feelings of social disconnection from baseline
Time Frame: At baseline and then at 2, 4, and 6 hours after LPS (or saline) administration
Feelings of Social Disconnection Scale: a self-report questionnaire of feelings of social disconnection with scores ranging from 0 to 28, with higher scores indicating more severe feelings of social disconnection
At baseline and then at 2, 4, and 6 hours after LPS (or saline) administration
Change in fatigue from baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Short Form of the Profile of Mood States (POMS-SF) Fatigue Subscale with higher scores indicating more severe fatigue (range 0-20)
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Change in confusion from baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Short Form of the Profile of Mood States (POMS) Confusion Subscale with higher scores indicating more severe confusion (range 0-20)
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Change in verbal memory from baseline
Time Frame: At baseline and then 3 hours after LPS (or saline) administration
Verbal memory measured using computerized tests from CNS Vital Signs™
At baseline and then 3 hours after LPS (or saline) administration
Change in visual memory from baseline
Time Frame: At baseline and then 3 hours after LPS (or saline) administration
Visual memory measured using computerized tests from CNS Vital Signs™
At baseline and then 3 hours after LPS (or saline) administration
Change in executive function from baseline
Time Frame: At baseline and then 3 hours after LPS (or saline) administration
Executive function measured using computerized tests from CNS Vital Signs™
At baseline and then 3 hours after LPS (or saline) administration
Change in attention from baseline
Time Frame: At baseline and then 3 hours after LPS (or saline) administration
Attention measured using computerized tests from CNS Vital Signs™
At baseline and then 3 hours after LPS (or saline) administration

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Subjective Sensitivity to Social Rejection
Time Frame: 2 hours after LPS (or saline) administration
Cyberball Social Exclusion Task
2 hours after LPS (or saline) administration
Negative Bias in Facial Emotion Recognition
Time Frame: 2 hours after LPS (or saline) administration
Emotional Face Recognition Task
2 hours after LPS (or saline) administration
Reward
Time Frame: 2 hours after LPS (or saline) administration
Reward Learning Task
2 hours after LPS (or saline) administration
Change in proinflammatory cytokines from baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Plasma proinflammatory cytokines (interleukin-1 receptor antagonist, interleukin-6, tumor necrosis factor-α, and soluble tumor necrosis factor receptor)
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Change in kynurenine Metabolites from baseline
Time Frame: At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Plasma tryptophan, kynurenine, quinolinic acid, and kynurenic acid
At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration
Change in gene expression from baseline
Time Frame: At baseline and 30 minutes after LPS (or saline) administration
Genome-wide transcriptional profiling with focus on the percentage increase from baseline to 30 minutes after LPS (or saline) administration in activities of transcription factors related to immune activation, sympathetic activation, and glucocorticoid insensitivity: respectively, nuclear factor kappa-B (NF-kB), cAMP response element-binding protein (CREB), and glucocorticoid receptor (GR).
At baseline and 30 minutes after LPS (or saline) administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, Los Angeles

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2023

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 10, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 16, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 5, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 3, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20-000005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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