Theophylline for Depression Study

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StatusBelum merekrut

Sponsor

University of California, Los Angeles

UJI KLINIS: NCT04309877

BioSeek: nct04309877

Kata kunci

Abstrak

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.

tanggal

Terakhir Diverifikasi:	02/29/2020
Pertama Dikirim:	03/09/2020
Perkiraan Pendaftaran Telah Dikirim:	03/11/2020
Pertama Diposting:	03/15/2020
Pembaruan Terakhir Dikirim:	03/11/2020
Pembaruan Terakhir Diposting:	03/15/2020
Tanggal Mulai Studi Sebenarnya:	02/29/2020
Perkiraan Tanggal Penyelesaian Utama:	05/31/2020
Perkiraan Tanggal Penyelesaian Studi:	05/31/2020

Kondisi atau penyakit

Depression

Intervensi / pengobatan

Drug: Theophylline ER

Other: PO placebo

Biological: Lipopolysaccharide (LPS)

Other: IV placebo

Tahap

Kelompok Lengan

Lengan	Intervensi / pengobatan
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
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
Experimental: PO theophylline & IV placebo PO theophylline 400 mg/day for 2 weeks followed by a single IV bolus of 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

Kriteria kelayakan

Usia yang Layak untuk Belajar	18 Years Untuk 18 Years
Jenis Kelamin yang Layak untuk Belajar	All
Menerima Relawan Sehat	Iya
Kriteria	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

Hasil

Ukuran Hasil Utama

1. 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)

Ukuran Hasil Sekunder

1. 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)

2. 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

3. 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

4. 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)

5. 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)

6. 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™

7. 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™

8. 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™

9. 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™

Ukuran Hasil Lainnya

1. Subjective Sensitivity to Social Rejection [2 hours after LPS (or saline) administration]

Cyberball Social Exclusion Task

2. Negative Bias in Facial Emotion Recognition [2 hours after LPS (or saline) administration]

Emotional Face Recognition Task

3. Reward [2 hours after LPS (or saline) administration]

Reward Learning Task

4. Change in proinflammatory cytokines from baseline [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)

5. Change in kynurenine Metabolites from baseline [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

6. Change in gene expression from baseline [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).

Theophylline for Depression Study

Kata kunci

theophylline

hepatitis c

radang

asma

hepatitis

obesitas

antidepresan