Trial Outcomes & Findings for Smell Changes & Efficacy of Nasal Theophylline (NCT NCT03990766)

NCT ID: NCT03990766

Last Updated: 2022-03-31

Results Overview

Self-reported change in smell after intervention on a 7-point Likert scale. Response options with corresponding point values: 7) Much better, 6) Somewhat better, 5) Slightly better, 4) Neither better nor worse, 3) Slightly worse, 2) Somewhat worse, and 1) Much worse. The maximum score is 7, and higher values indicate better outcomes. A score of 4 is considered neutral. Scores of 5 or higher indicated clinical improvement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

6 weeks

Results posted on

2022-03-31

Participant Flow

Participant milestones

Participant milestones
Measure
Theophylline
12 mg of theophylline dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Placebo
Lactose capsule contents dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Overall Study
STARTED
14
13
Overall Study
COMPLETED
12
10
Overall Study
NOT COMPLETED
2
3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Smell Changes & Efficacy of Nasal Theophylline

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Theophylline Saline Irrigation
n=12 Participants
Theophylline 12 mg capsule contents dissolved into a sinus rinse bottle containing distilled or boiled tap water and USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets, delivered to the bilateral nasal cavities twice daily. Theophylline: Theophylline delivered via high-volume, low-pressure nasal saline irrigation
Placebo Saline Irrigation
n=10 Participants
Identical-appearing lactose monohydrate capsule contents dissolved into a sinus rinse bottle containing distilled or boiled tap water and USP Grade Sodium Chloride \& Sodium Bicarbonate Mixture commercially prepared packets, delivered to the bilateral nasal cavities twice daily. Saline Nasal: Lactose delivered via high-volume, low-pressure nasal saline irrigation
Total
n=22 Participants
Total of all reporting groups
Age, Continuous
57.5 years
n=113 Participants
59.5 years
n=163 Participants
59.0 years
n=160 Participants
Sex: Female, Male
Female
8 Participants
n=113 Participants
6 Participants
n=163 Participants
14 Participants
n=160 Participants
Sex: Female, Male
Male
4 Participants
n=113 Participants
4 Participants
n=163 Participants
8 Participants
n=160 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=113 Participants
0 Participants
n=163 Participants
0 Participants
n=160 Participants
Race (NIH/OMB)
Asian
0 Participants
n=113 Participants
0 Participants
n=163 Participants
0 Participants
n=160 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=113 Participants
0 Participants
n=163 Participants
0 Participants
n=160 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=113 Participants
1 Participants
n=163 Participants
2 Participants
n=160 Participants
Race (NIH/OMB)
White
11 Participants
n=113 Participants
9 Participants
n=163 Participants
20 Participants
n=160 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=113 Participants
0 Participants
n=163 Participants
0 Participants
n=160 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=113 Participants
0 Participants
n=163 Participants
0 Participants
n=160 Participants
Region of Enrollment
United States
12 participants
n=113 Participants
10 participants
n=163 Participants
22 participants
n=160 Participants
Body Mass Index
32.3 kg/m^2
n=113 Participants
33.0 kg/m^2
n=163 Participants
33.0 kg/m^2
n=160 Participants
Smoking history
0 Participants
n=113 Participants
2 Participants
n=163 Participants
2 Participants
n=160 Participants
Deviated septum
3 Participants
n=113 Participants
2 Participants
n=163 Participants
5 Participants
n=160 Participants
Diabetes mellitus
1 Participants
n=113 Participants
1 Participants
n=163 Participants
2 Participants
n=160 Participants
Obstructive sleep apnea on positive airway pressure
2 Participants
n=113 Participants
0 Participants
n=163 Participants
2 Participants
n=160 Participants
Hypothyroidism
3 Participants
n=113 Participants
1 Participants
n=163 Participants
4 Participants
n=160 Participants
Family history of dementia
2 Participants
n=113 Participants
1 Participants
n=163 Participants
3 Participants
n=160 Participants
Moderate/severe comorbidity (ACE-27 scores 2-3)
5 Participants
n=113 Participants
1 Participants
n=163 Participants
6 Participants
n=160 Participants
Prior oral steroids
8 Participants
n=113 Participants
6 Participants
n=163 Participants
14 Participants
n=160 Participants
Prior nasal steroids
9 Participants
n=113 Participants
7 Participants
n=163 Participants
16 Participants
n=160 Participants
Prior olfactory training
1 Participants
n=113 Participants
2 Participants
n=163 Participants
3 Participants
n=160 Participants
Time from upper respiratory infection to treatment
11.0 months
n=113 Participants
8.4 months
n=163 Participants
8.8 months
n=160 Participants

PRIMARY outcome

Timeframe: 6 weeks

Self-reported change in smell after intervention on a 7-point Likert scale. Response options with corresponding point values: 7) Much better, 6) Somewhat better, 5) Slightly better, 4) Neither better nor worse, 3) Slightly worse, 2) Somewhat worse, and 1) Much worse. The maximum score is 7, and higher values indicate better outcomes. A score of 4 is considered neutral. Scores of 5 or higher indicated clinical improvement.

Outcome measures

Outcome measures
Measure
Theophylline
n=12 Participants
12 mg of theophylline dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Placebo
n=10 Participants
Lactose capsule contents dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Number of Patients With Improvement in Global Rating of Smell Change
4 Participants
3 Participants

SECONDARY outcome

Timeframe: 6 weeks

Within- and between-subject changes in UPSIT total scores measured at baseline and at 6 weeks after therapy. This test is a validated 40-question forced-choice odor identification test where microencapsulated odorants on a strip are released by scratching. Each question corresponds to one point, and there are no subscales. The minimum score is 0 while the maximum score is 40, and higher values indicate better outcomes.

Outcome measures

Outcome measures
Measure
Theophylline
n=12 Participants
12 mg of theophylline dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Placebo
n=10 Participants
Lactose capsule contents dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
University of Pennsylvania Smell Identification Test (UPSIT) Total Score Change
1 score on a scale
Interval -4.0 to 12.0
0 score on a scale
Interval -8.0 to 5.0

SECONDARY outcome

Timeframe: 6 weeks

Within- and between-subject changes in QOD-NS scores measured at baseline and at 6 weeks after therapy, which is a validated 17-item questionnaire about quality of life and impairments related to olfactory dysfunction. Each question is scored from 0 to 3 points, and there are no subscales. The minimum score is 0 while the maximum score is 51, and higher values indicate worse quality of life or higher degree of impairment.

Outcome measures

Outcome measures
Measure
Theophylline
n=12 Participants
12 mg of theophylline dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Placebo
n=10 Participants
Lactose capsule contents dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) Score Change
-6.5 score on a scale
Interval -15.0 to 4.0
1.5 score on a scale
Interval -4.0 to 19.0

SECONDARY outcome

Timeframe: 6 weeks

Within- and between-subject changes measured at baseline and at 6 weeks after therapy. This test is a new disease-specific 28-item questionnaire that assesses for physical, functional, and emotional limitations in patients with olfactory dysfunction of any etiology. Each question is scored from 0 to 4. The minimum score is 0 while the maximum score is 112, and higher values indicate higher degree of limitations and worse outcomes. There are no subscales within the current questionnaire.

Outcome measures

Outcome measures
Measure
Theophylline
n=12 Participants
12 mg of theophylline dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Placebo
n=10 Participants
Lactose capsule contents dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Olfactory Dysfunction Outcomes Ratings (ODOR) Score Change
-1.5 score on a scale
Interval -18.0 to 6.0
-7.5 score on a scale
Interval -29.0 to 6.0

Adverse Events

Theophylline

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Theophylline
n=14 participants at risk
12 mg of theophylline dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Placebo
n=13 participants at risk
Lactose capsule contents dissolved in 240 mL of saline, administered to the bilateral nasal cavities twice a day for 6 weeks
Blood and lymphatic system disorders
Detectable serum theophylline
0.00%
0/5 • Adverse event data were collected over 6 weeks of treatment
The first 10 participants regardless of intervention underwent theophylline level measurements after 1 week of treatment. If a measurable amount of theophylline was identified, the test would be immediately repeated. If theophylline was detected in the second sample, the plan was to continue measuring in another 10 subjects. In addition, all participants were queried biweekly regarding any adverse effects.
0.00%
0/5 • Adverse event data were collected over 6 weeks of treatment
The first 10 participants regardless of intervention underwent theophylline level measurements after 1 week of treatment. If a measurable amount of theophylline was identified, the test would be immediately repeated. If theophylline was detected in the second sample, the plan was to continue measuring in another 10 subjects. In addition, all participants were queried biweekly regarding any adverse effects.

Additional Information

Dr. Jake Lee

Washington University School of Medicine

Phone: 3143937248

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place