HONORR: Helping Olfaction and Nutrition On Renal Replacement

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02479451

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
End Stage Renal Disease Olfactory Disorders	Drug: Theophylline	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Helping Olfaction and Nutrition On Renal Replacement

Actual Study Start Date :

Oct 1, 2015

Actual Primary Completion Date :

Jul 1, 2022

Actual Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nasal 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	Drug: Theophylline The study medication will be provided by Foundation Care.

Arm

Intervention/Treatment

Experimental: Nasal 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

Drug: Theophylline

The study medication will be provided by Foundation Care.

Outcome Measures

Primary Outcome Measures

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 will be administered by study investigators. Score ranges between 0 and 40.
Change from baseline in smell threshold test score at 6 weeks [Baseline and every 2 weeks for 6 weeks]
This test determines lowest concentration of an odor compound that is perceivable by study participants. Score ranges between 2 and 10.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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