Theophylline for Depression Study

Early Phase 1

Withdrawn

• Conditions: Depression
• Interventions: Drug: Theophylline ER; Other: PO placebo; Other: IV placebo; Biological: Lipopolysaccharide (LPS)

• Registration Number: NCT04309877
• Lead Sponsor: University of California, Los Angeles

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-03-10
• Study First Submitted QC: 2020-03-12
• Study First Posted: 2020-03-16
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-03
• Last Update Posted: 2021-11-05
• Study Start: 2023-03
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
PO theophylline & IV LPS	Theophylline ER	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
PO placebo & IV placebo	IV placebo	PO methylcellulose (placebo) daily for 2 weeks followed by a single IV bolus of 0.9% saline
PO placebo & IV placebo	PO placebo	PO methylcellulose (placebo) daily for 2 weeks followed by a single IV bolus of 0.9% saline
PO theophylline & IV LPS	Lipopolysaccharide (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
PO theophylline & IV placebo	Theophylline ER	PO theophylline 400 mg/day for 2 weeks followed by a single IV bolus of 0.9% saline
PO placebo & IV LPS	Lipopolysaccharide (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
PO placebo & IV LPS	PO placebo	PO methylcellulose (placebo) daily for 2 weeks followed by a single intravenous (IV) bolus of lipopolysaccharide (LPS) 0.8 ng/kg of body weight
PO theophylline & IV placebo	IV placebo	PO theophylline 400 mg/day for 2 weeks followed by a single IV bolus of 0.9% saline

Primary Outcome Measures

Name	Time	Method
Change in depressed mood from baseline	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)

Secondary Outcome Measures

Name	Time	Method
Change in depressive symptoms from baseline	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
Change in verbal memory from baseline	At baseline and then 3 hours after LPS (or saline) administration	Verbal memory measured using computerized tests from CNS Vital Signs™
Change in executive function from baseline	At baseline and then 3 hours after LPS (or saline) administration	Executive function measured using computerized tests from CNS Vital Signs™
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	Short Form of the Profile of Mood States (POMS-SF) Tension Subscale with higher scores indicating more severe tension/anxiety (range 0-24)
Change in feelings of social disconnection from baseline	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
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	Short Form of the Profile of Mood States (POMS-SF) Fatigue Subscale with higher scores indicating more severe fatigue (range 0-20)
Change in attention from baseline	At baseline and then 3 hours after LPS (or saline) administration	Attention measured using computerized tests from CNS Vital Signs™
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	Short Form of the Profile of Mood States (POMS) Confusion Subscale with higher scores indicating more severe confusion (range 0-20)
Change in visual memory from baseline	At baseline and then 3 hours after LPS (or saline) administration	Visual memory measured using computerized tests from CNS Vital Signs™

Trial Locations

Locations (1)

UCLA Cousins Center for Psychoneuroimmunology; 🇺🇸 Los Angeles, California, United States