Helping Olfaction and Nutrition On Renal Replacement

Study Overview
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Brief Summary
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This clinical trial examines whether nasal theophylline administration can improve olfaction and nutrition in hemodialysis patients.

Detailed Description
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Malnutrition and cachexia are prevalent in end stage renal disease (ESRD) patients and are associated with increased morbidity and mortality. Food aversion is a major contributor to anorexia and malnutrition in ESRD and it also impacts the quality of life. Olfactory dysfunction has been shown to contribute to food aversion in ESRD patients. Since up to 80% of a meal's flavor is attributed to olfactory input, loss or alteration of smell leads to loss or alteration of taste in ESRD patients and at present there are no effective therapies to treat smell and/or taste disorders in ESRD patients. In patients with other causes of olfactory dysfunction such as congenital hyposmia and traumatic brain injury, intranasal theophylline has been shown to be effective in improving olfactory defects via increasing nasal mucus levels of cAMP and cGMP, second messengers critical for optimal smell sensation. However, the efficacy of nasal theophylline to improve olfaction in ESRD patients has not been investigated and the effects of nasal theophylline treatment on the nutritional parameters are unknown in ESRD patients. Aim: To examine the efficacy and safety of nasal theophylline treatment to improve olfaction and nutrition in ESRD patients Hypothesis: Nasal theophylline treatment improves olfaction and nutrition in ESRD patients with olfactory defects by via increasing intracellular cAMP and cGMP levels. A previous pilot clinical trial demonstrated that intranasal theophylline is safe and effective in improving olfactory deficits in congenital hyposmia and traumatic brain injury, however, it has not been examined in ESRD patients. The investigators will conduct a pilot single arm open-label clinical trial (n=20) of 6 weeks duration to examine the efficacy and safety of nasal theophylline in hemodialysis-dependent ESRD patients with olfactory defects. The investigators will examine whether nasal theophylline improves olfaction and nutritional status in trial participants.

Official Title
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Helping Olfaction and Nutrition On Renal Replacement

Conditions
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End Stage Renal Disease, Olfactory Disorders

Intervention / Treatment
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* Drug: Theophylline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ESRD requiring chronic outpatient hemodialysis Able to provide written consent Defects in smell identification and/or smell threshold detection as measured by Scratch-and-sniff University of Pennsylvania Smell Identification Test (UPSIT) and Smell Threshold Test Exclusion Criteria: Prior allergic reaction to theophylline Patients currently treated with theophylline for clinical indication Pregnancy or lactation ESRD patients on peritoneal dialysis Patients hospitalized at the time of study enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nasal theophylline<br>20 μg intranasal theophylline (theophylline methylpropyl paraben in a 0.4-mL saline solution) once daily (in the morning) into each naris for a total of 6 weeks | Drug: Theophylline<br>* The study medication will be provided by Foundation Care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in smell identification test score at 6 weeks | Smell identification test is a validated 40-item scratch and sniff smell identification test that will be administered by study investigators. Score ranges between 0 and 40. | Baseline and every 2 weeks for 6 weeks | 
| Change from baseline in smell threshold test score at 6 weeks | This test determines lowest concentration of an odor compound that is perceivable by study participants. Score ranges between 2 and 10. | Baseline and every 2 weeks for 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in serum albumin level at 6 weeks | Serum albumin is one of the markers of nutritional status. | Baseline and 6 weeks | 
| Change from baseline in serum prealbumin level at 6 weeks | Serum prealbumin is one of the markers of nutritional status. | Baseline and 6 weeks | 
| Change from baseline in serum triglyceride level at 6 weeks | Serum triglyceride is one of the markers of nutritional status. | Baseline and 6 weeks | 
| Change from baseline in serum transferrin level at 6 weeks | Serum transferrin is one of the markers of nutritional status. | Baseline and 6 weeks | 
| Change from baseline in nasal mucus cAMP level at 6 weeks | Nasal cAMP is an important mediator of smell sensation. It will be measured using an ELISA assay. | Baseline and 6 weeks | 
| Change from baseline in salivary cAMP level at 6 weeks | Salivary cAMP is an important mediator of smell sensation. It will be measured using an ELISA assay. | Baseline and 6 weeks | 
| Change from baseline in nasal mucus cGMP level at 6 weeks | Nasal cGMP is an important mediator of smell sensation. It will be measured using an ELISA assay. | Baseline and 6 weeks | 
| Change from baseline in salivary cGMP level at 6 weeks | Salivary cGMP is an important mediator of smell sensation. It will be measured using an ELISA assay. | Baseline and 6 weeks | 
| Change from baseline in plasma theophylline level at 6 weeks | Plasma levels of theophylline will be measured using fluorescence polarization technique. | Baseline and every 2 weeks for 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End stage renal disease, Olfaction, Dialysis, Hemodialysis, Malnutrition