Theophylline for Depression Study

NCT04309877 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 20-000005
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Change in depressed mood from baseline

  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 Outcomes (9)

• Change in tension/anxiety from baseline

  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

  At baseline and then at 2, 4, and 6 hours after LPS (or saline) administration

• Change in feelings of social disconnection from baseline

  At baseline and then at 2, 4, and 6 hours after LPS (or saline) administration

• Change in fatigue from baseline

  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

  At baseline and then at 1, 1.5, 2, 3, 4, 5, and 6 hours after LPS (or saline) administration

Other Outcomes (6)

• Subjective Sensitivity to Social Rejection

  2 hours after LPS (or saline) administration

• Negative Bias in Facial Emotion Recognition

  2 hours after LPS (or saline) administration

• Reward

  2 hours after LPS (or saline) administration

Study Arms (4)

PO theophylline & IV LPS

EXPERIMENTAL

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; Biological: Lipopolysaccharide (LPS)

PO placebo & IV LPS

EXPERIMENTAL

PO methylcellulose (placebo) daily for 2 weeks followed by a single intravenous (IV) bolus of lipopolysaccharide (LPS) 0.8 ng/kg of body weight

Other: PO placebo; Biological: Lipopolysaccharide (LPS)

PO theophylline & IV placebo

EXPERIMENTAL

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

Drug: Theophylline ER; Other: IV placebo

PO placebo & IV placebo

PLACEBO COMPARATOR

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

Other: PO placebo; Other: IV placebo

Interventions

Theophylline ER DRUG

Capsules of theophylline ER

PO theophylline & IV LPS; PO theophylline & IV placebo

PO placebo OTHER

Capsules of methylcellulose

PO placebo & IV LPS; PO placebo & IV placebo

Lipopolysaccharide (LPS) BIOLOGICAL

Purified bacterial wall component as an inflammatory challenge

PO placebo & IV LPS; PO theophylline & IV LPS

IV placebo OTHER

Normal (0.9%) saline

PO placebo & IV placebo; PO theophylline & IV placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead

Study Sites (1)

UCLA Cousins Center for Psychoneuroimmunology

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Depression

Interventions

Lipopolysaccharides

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Endotoxins; Bacterial Toxins; Toxins, Biological

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: March 10, 2020
• First Posted: March 16, 2020
• Study Start: March 1, 2023
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: November 5, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)