Pilot Randomized Controlled Trial of Theophylline for Attenuation of Lipopolysaccharide-Induced Depressive Symptoms
Overview
- Phase
- Early Phase 1
- Intervention
- PO placebo
- Conditions
- Depression
- Sponsor
- University of California, Los Angeles
- Locations
- 1
- Primary Endpoint
- Change in depressed mood from baseline
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
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.
Investigators
Hyong Jin Cho
Associate professor
University of California, Los Angeles
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
Arms & Interventions
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
Intervention: PO placebo
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
Intervention: Theophylline ER
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
Intervention: Lipopolysaccharide (LPS)
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
Intervention: Lipopolysaccharide (LPS)
PO theophylline & IV placebo
PO theophylline 400 mg/day for 2 weeks followed by a single IV bolus of 0.9% saline
Intervention: Theophylline ER
PO theophylline & IV placebo
PO theophylline 400 mg/day for 2 weeks followed by a single IV bolus of 0.9% saline
Intervention: IV placebo
PO placebo & IV placebo
PO methylcellulose (placebo) daily for 2 weeks followed by a single IV bolus of 0.9% saline
Intervention: PO placebo
PO placebo & IV placebo
PO methylcellulose (placebo) daily for 2 weeks followed by a single IV bolus of 0.9% saline
Intervention: IV placebo
Outcomes
Primary Outcomes
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)
Secondary Outcomes
- Change in depressive symptoms from baseline(At baseline and then at 2, 4, and 6 hours after LPS (or saline) administration)
- Change in verbal memory from baseline(At baseline and then 3 hours after LPS (or saline) administration)
- Change in executive function from baseline(At baseline and then 3 hours after LPS (or saline) administration)
- 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 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 attention from baseline(At baseline and then 3 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)
- Change in visual memory from baseline(At baseline and then 3 hours after LPS (or saline) administration)