End Stage Renal Disease, Olfactory Disorders
Conditions
Keywords
End stage renal disease, Olfaction, Dialysis, Hemodialysis, Malnutrition
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.
Interventions
DRUGTheophylline
The study medication will be provided by Foundation Care.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Theophylline: The study medication will be provided by Foundation Care. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Nasal Theophylline |
|---|---|
| Age, Continuous | 55 years |
| ESRD | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
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 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.
Time frame: Baseline and every 2 weeks for 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nasal Theophylline | Change From Baseline in Smell Identification Test Score at 6 Weeks | 4 units on a scale | Standard Error 2 |
Primary
Change From Baseline in Smell Threshold Test Score at 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.
Time frame: Baseline and every 2 weeks for 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nasal Theophylline | Change From Baseline in Smell Threshold Test Score at 6 Weeks | -1 change in score on the scale | Standard Error 2 |
Secondary
Change From Baseline in Plasma Theophylline Level at 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.
Time frame: Baseline and every 2 weeks for 6 weeks
Population: Serum theophylline levels assessed at every follow-up were undetectable throughout the study period in all participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nasal Theophylline | Change From Baseline in Plasma Theophylline Level at 6 Weeks | 0 microgram/mL | Standard Deviation 0 |