Helping Olfaction and Nutrition On Renal Replacement

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.

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