Helping Olfaction and Nutrition On Renal Replacement

Phase 2

Completed

Conditions: Olfactory Disorders
End Stage Renal Disease

Interventions: Drug: Theophylline

Registration Number: NCT02479451

Lead Sponsor: Massachusetts General Hospital

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nasal theophylline	Theophylline	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

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Smell Identification Test Score at 6 Weeks	Baseline and every 2 weeks for 6 weeks	Smell identification test is a validated 40-item scratch and sniff smell identification test that was administered by study investigators. Scores on this test scale range between 0 (minimum) to 40 (maximum). Higher score indicates better ability for smell identification. Total scores are reported on this scale (no sub-scales). The unit is score on this scale.
Change From Baseline in Smell Threshold Test Score at 6 Weeks	Baseline and every 2 weeks for 6 weeks	This test determined the lowest concentration of an odor compound that is perceivable by study participants. Scores on this test scale range between -2 and -10. Higher score indicates higher smell detection threshold (i.e. worse ability to smell). Total scores are reported on this scale (no sub-scales). The unit is score on this scale.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Plasma Theophylline Level at 6 Weeks	Baseline and every 2 weeks for 6 weeks	Plasma levels of theophylline were measured using fluorescence polarization technique. Minimum level will be 0 microgram/mL and maximum assay limit is 40 microgram/mL. Higher levels indicate increased systemic exposure to theophylline. Units on scale are microgram/mL.