Smell in Covid-19 and Efficacy of Nasal Theophylline
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- UPSIT
研究概览
简要总结
Evidence of COVID-19 related anosmia and dysgeusia continues to accumulate daily.
Currently, up to 80% of patients report subjective olfactory dysfunction (OD), and prevalence using objective olfactory testing could be even higher.
We propose a phase II single-site, double-blinded, placebo-controlled randomized clinical trial to determine the efficacy and safety of intranasal theophylline, a known phosphodiesterase inhibitor in the treatment of asthma, as a possible treatment for COVID-19 related OD. Theophylline has shown benefit in similar clinical trials for post-viral OD.
详细描述
Post-viral olfactory dysfunction has numerous known adverse effects such as loss of cortical gray matter and decrease in quality of life. COVID-19 related olfactory dysfunction has already been shown to be correlated with depression and decreased quality of life, so finding an effective treatment is imperative.
Intranasal and oral corticosteroids as well as olfactory training are currently used to treat post-viral OD; however they have demonstrated limited efficacy and there is no current gold standard of care. There is no current consensus on the pathogenesis of COVID-related anosmia; however evidence for post-viral olfactory dysfunction suggests sensory axonal regeneration and olfactory signaling may rely on elevated levels of secondary messengers cAMP and cGMP, a known effect of theophylline. In this phase II treatment trial, patients will be allocated 1:1 to receive either intranasal theophylline irrigation or placebo for six weeks. Various smell surveys and scratch-and-sniff tests will be utilized to capture changes in smell ability.
Due to COVID-19, this study will be conducted virtually, except for the first ten enrolled patients who will undergo one serum theophylline test. This study is limited to patients living in Missouri or Illinois.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
The pharmacy will maintain the blind until the completion of the study.
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Olfactory dysfunction that has persisted for >3 months following suspected COVID-19 infection
- •Residing within the states of Missouri or Illinois.
- •Can read, write, and understand English.
排除标准
- •History of olfactory dysfunction prior to COVID-19 infection
- •Use of concomitant therapies specifically for the treatment of olfactory dysfunction
- •History of olfactory dysfunction longer than 12 months
- •Known existence of nasal polyps, prior sinonasal, or anterior skull-based surgery
- •Dependence on theophylline for comorbid conditions such as asthma and COPD
- •History of an allergic reaction to theophylline or other methylxanthines
- •History of neurodegenerative disease (ie. Alzheimer's dementia, Parkinson's disease, Lewy body dementia, frontotemporal dementia)
- •Pregnant or breastfeeding mothers
- •Current use of medications with significant interactions with theophylline, which include cimetidine, ciprofloxacin, disulfiram, enoxacin, fluvoxamine, interferon-alpha, lithium, mexiletine, phenytoin, propafenone, propranolol, tacrine, thiabendazole, ticlopidine, and troleandomycin.
- •Pre-existing arrhythmias or seizures
研究组 & 干预措施
Theophylline
400mg theophylline capsule diluted in 240 mL isotonic nasal saline lavage twice daily for six weeks.
干预措施: Theophylline Powder (Drug)
Placebo
500mg lactose capsule diluted in 240 mL isotonic nasal saline lavage twice daily for six weeks.
干预措施: Placebo Comparator (Drug)
结局指标
主要结局
UPSIT
时间窗: Comparison of response rate at 6 weeks post-intervention from baseline between the 2 study groups
UPSIT 0-40 with higher scores indicating better results. The response rate defined as the number of participants in each group self-reporting of at least slightly better improvement in the Clinical Global Improvement Scale at 6 weeks post intervention as compared to baseline, devided by the total number of participants in that specific group. The CGI-Improvement Scale has seven response options (from 1 as Very Much Improved to 7 as Very Much Worsened) for answers to the question "Compared to your sense of smell before you started the nasal irrigations, how would you rate your sense of smell now" . Participants reporting 3 as "Minimally Improved", 2 as "Much Improved", or 1 as "Very Much Improved" in the CGI-I will be deemed responders to treatment, and the rate of responders will be compared between the two arms.
次要结局
- Change in Questionnaire for Olfactory Dysfunction (QOD) From Baseline to 6 Weeks Post Intervention(Comparison at 6 weeks post-intervention from baseline)
- Olfactory Dysfunction Outcomes Rating (ODOR)(Comparison of response rate at 6 weeks post-intervention from baseline between the 2 study groups)
- 36-Item Short Form Health Survey (SF-36)(Baseline assessment)
- University of Pennsylvania Smell Identification Test (UPSIT)(Comparison at 6 weeks post-intervention from baseline)