Theophylline for Depression Study

NCT ID: NCT04309877

Last Updated: 2021-11-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-31
• Study Completion Date: 2025-06-30

Brief Summary

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.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Theophylline ER

Intervention Type: DRUG

Capsules of theophylline ER

Lipopolysaccharide (LPS)

Intervention Type: BIOLOGICAL

Purified bacterial wall component as an inflammatory challenge

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

Group Type: EXPERIMENTAL

PO placebo

Intervention Type: OTHER

Capsules of methylcellulose

Lipopolysaccharide (LPS)

Intervention Type: BIOLOGICAL

Purified bacterial wall component as an inflammatory challenge

PO theophylline & IV placebo

PO theophylline 400 mg/day for 2 weeks followed by a single IV bolus of 0.9% saline

Group Type: EXPERIMENTAL

Theophylline ER

Intervention Type: DRUG

Capsules of theophylline ER

IV placebo

Intervention Type: OTHER

Normal (0.9%) saline

PO placebo & IV placebo

PO methylcellulose (placebo) daily for 2 weeks followed by a single IV bolus of 0.9% saline

Group Type: PLACEBO_COMPARATOR

PO placebo

Intervention Type: OTHER

Capsules of methylcellulose

IV placebo

Intervention Type: OTHER

Normal (0.9%) saline

Interventions

Theophylline ER

Capsules of theophylline ER

Intervention Type: DRUG

PO placebo

Capsules of methylcellulose

Intervention Type: OTHER

Lipopolysaccharide (LPS)

Purified bacterial wall component as an inflammatory challenge

Intervention Type: BIOLOGICAL

IV placebo

Normal (0.9%) saline

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Hyong Jin Cho

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UCLA Cousins Center for Psychoneuroimmunology

Los Angeles, California, United States

Countries

United States

Other Identifiers

20-000005

Identifier Type: -

Identifier Source: org_study_id