Trial Outcomes & Findings for Efficacy of Gabapentin for Post-Covid-19 Olfactory Dysfunction (NCT NCT05184192)
NCT ID: NCT05184192
Last Updated: 2025-03-04
Results Overview
The primary outcome measure was the treatment response rate following the 8-week FD phase as determined by the CGI-I. The CGI-I is a modified 7-point Likert scale of -perceived change. Response options include: (1) much better, (2) somewhat better, (3) slightly better), (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, (7) much worse. The response rate was defined as the number of participants self-reporting at least "slightly better" divided by the number of participants in each treatment group. Th
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
68 participants
Primary outcome timeframe
After the 8 week FD phase and four week post-tapper
Results posted on
2025-03-04
Participant Flow
Participant milestones
| Measure |
Gabapentin
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
Overall Study
STARTED
|
34
|
34
|
|
Overall Study
COMPLETED
|
26
|
17
|
|
Overall Study
NOT COMPLETED
|
8
|
17
|
Reasons for withdrawal
| Measure |
Gabapentin
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
4
|
7
|
|
Overall Study
Adverse Event
|
1
|
4
|
|
Overall Study
PI withdrawal
|
1
|
2
|
|
Overall Study
Withdrew due to adverse effect
|
1
|
0
|
|
Overall Study
Medication schedule
|
1
|
0
|
|
Overall Study
Concern for adverse effects
|
0
|
4
|
Baseline Characteristics
Seven participants withdrew prior to baseline survey completion.
Baseline characteristics by cohort
| Measure |
Gabapentin
n=34 Participants
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=34 Participants
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
Total
n=68 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42 years
STANDARD_DEVIATION 10.6 • n=34 Participants
|
44 years
STANDARD_DEVIATION 15.5 • n=34 Participants
|
43 years
STANDARD_DEVIATION 13.5 • n=68 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=34 Participants
|
25 Participants
n=34 Participants
|
51 Participants
n=68 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=34 Participants
|
9 Participants
n=34 Participants
|
17 Participants
n=68 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
2 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Race (NIH/OMB)
White
|
23 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
33 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
56 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
0 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
1 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
3 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Race/Ethnicity, Customized
White
|
23 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
33 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
56 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
Race/Ethnicity, Customized
Black / African American
|
2 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
0 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
2 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
Race/Ethnicity, Customized
Hispanic
|
0 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
1 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
1 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
0 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
2 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
Region of Enrollment
United States
|
34 participants
n=34 Participants
|
34 participants
n=34 Participants
|
68 participants
n=68 Participants
|
|
University of Pennsylvania Smell Identification Test (UPSIT)
|
24.5 score on a scale (0-40)
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
25.5 score on a scale (0-40)
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
25.0 score on a scale (0-40)
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
Olfactory Dysfunction Outcomes Rating (ODOR)
|
56 score on a scale (0-112)
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
54.5 score on a scale (0-112)
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
56 score on a scale (0-112)
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
NASAL-7 categories
Anosmia (0-4)
|
9 Participants
n=27 Participants • 7 patients were excluded and not analyzed as previously explained.
|
11 Participants
n=34 Participants • 7 patients were excluded and not analyzed as previously explained.
|
20 Participants
n=61 Participants • 7 patients were excluded and not analyzed as previously explained.
|
|
NASAL-7 categories
Severe dysfunction (5-7)
|
12 Participants
n=27 Participants • 7 patients were excluded and not analyzed as previously explained.
|
16 Participants
n=34 Participants • 7 patients were excluded and not analyzed as previously explained.
|
28 Participants
n=61 Participants • 7 patients were excluded and not analyzed as previously explained.
|
|
NASAL-7 categories
Mild dysfunction (8-10)
|
4 Participants
n=27 Participants • 7 patients were excluded and not analyzed as previously explained.
|
5 Participants
n=34 Participants • 7 patients were excluded and not analyzed as previously explained.
|
9 Participants
n=61 Participants • 7 patients were excluded and not analyzed as previously explained.
|
|
NASAL-7 categories
Normosmia (11-14)
|
2 Participants
n=27 Participants • 7 patients were excluded and not analyzed as previously explained.
|
2 Participants
n=34 Participants • 7 patients were excluded and not analyzed as previously explained.
|
4 Participants
n=61 Participants • 7 patients were excluded and not analyzed as previously explained.
|
|
CGI-S of smell
Absent
|
6 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
5 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
11 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
CGI-S of smell
Poor
|
17 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
20 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
37 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
CGI-S of smell
Fair
|
3 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
7 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
10 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
CGI-S of smell
Good
|
1 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
1 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
2 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
CGI-S of smell
Very good
|
0 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
1 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
1 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
CGI-S of smell
Excellent
|
0 Participants
n=27 Participants • 7 participants withdrew prior to the baseline survey completion.
|
0 Participants
n=34 Participants • 7 participants withdrew prior to the baseline survey completion.
|
0 Participants
n=61 Participants • 7 participants withdrew prior to the baseline survey completion.
|
|
CGI-S of parosmia
Complete distortion
|
9 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
9 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
18 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
CGI-S of parosmia
Mostly distorted
|
13 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
10 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
23 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
CGI-S of parosmia
Moderate distortion
|
5 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
9 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
14 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
CGI-S of parosmia
Mild distortion
|
0 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
4 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
4 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
|
CGI-S of parosmia
No distortion
|
0 Participants
n=27 Participants • Seven participants withdrew prior to baseline survey completion.
|
2 Participants
n=34 Participants • Seven participants withdrew prior to baseline survey completion.
|
2 Participants
n=61 Participants • Seven participants withdrew prior to baseline survey completion.
|
PRIMARY outcome
Timeframe: After the 8 week FD phase and four week post-tapperPopulation: 26 participants in the placebo group completed the treatment, but 25 participants completed the posttaper survey.
The primary outcome measure was the treatment response rate following the 8-week FD phase as determined by the CGI-I. The CGI-I is a modified 7-point Likert scale of -perceived change. Response options include: (1) much better, (2) somewhat better, (3) slightly better), (4) neither better nor worse, (5) slightly worse, (6) somewhat worse, (7) much worse. The response rate was defined as the number of participants self-reporting at least "slightly better" divided by the number of participants in each treatment group. Th
Outcome measures
| Measure |
Gabapentin
n=18 Participants
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=32 Participants
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
Clinical Global Impression of Improvement Scale (CGI-I)
Fixed Dose Period
|
8 Participants
|
20 Participants
|
|
Clinical Global Impression of Improvement Scale (CGI-I)
4 week post tapper
|
7 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down periodPopulation: 26 participants in placebo group completed treatment, but 25 participants completed the posttaper survey. 18 participants in the gabapentin group completed treatment, but 16 participants completed the post-taper survey.
Forty different odors are presented in this test. Scoring: Forced choice of 4 responses to identify each smell. Anosmia: score 6-18; severe microsmia: score 19-25, moderate microsmia: 26-30 in women and 26-29 in men; mild microsmia: 31-34 in women and 30-33 in men; and normosmia: score \> 34 in women and \>33 in men. The total UPSIT score can range from 0 to 40 and scores. The MCID in UPSIT score is 4. Scores are interpreted as the level of absolute smell function (i.e., normosmia, mild hyposmia, moderate hyposmia, severe hyposmia, and anosmia), using the age- and sex-related normative classification system described in the UPSIT manual (Table 1)
Outcome measures
| Measure |
Gabapentin
n=18 Participants
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=26 Participants
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
University of Pennsylvania Smell Identification Test (UPSIT)
Baseline
|
23 score on a scale (0-40)
Interval 10.0 to 31.0
|
24 score on a scale (0-40)
Interval 7.0 to 34.0
|
|
University of Pennsylvania Smell Identification Test (UPSIT)
Fixed Dose
|
25 score on a scale (0-40)
Interval 12.0 to 34.0
|
25 score on a scale (0-40)
Interval 15.0 to 34.0
|
|
University of Pennsylvania Smell Identification Test (UPSIT)
Post-taper
|
26 score on a scale (0-40)
Interval 7.0 to 33.0
|
25 score on a scale (0-40)
Interval 9.0 to 35.0
|
SECONDARY outcome
Timeframe: Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down periodPopulation: 26 participants in placebo group completed treatment, but 25 participants completed the posttaper survey. 18 participants in the gabapentin group completed treatment, but 16 participants completed the post-taper survey. Each of the 28 items is scored 0 to 4. The maximum total score is 112 with higher scores representing greater quality of life impairment. The MCID is 15.
The ODOR questionnaire is a validated 28-item patient-reported outcome measure which assesses the physical, functional, and emotional consequences of OD. The ODOR is a 28-item instrument with each item scored as either no difficulty or very rarely bothered (0) to complete difficulty or very frequently bothered (4) with a total instrument score range of 0 to 112 points. Higher scores indicate higher degree of dysfunction and limitation. the MCID is 15 points.
Outcome measures
| Measure |
Gabapentin
n=18 Participants
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=26 Participants
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
Olfactory Dysfunction Outcomes Rating (ODOR)
Baseline
|
23 score on a scale (0-112)
Interval 10.0 to 31.0
|
54.5 score on a scale (0-112)
Interval 30.0 to 96.0
|
|
Olfactory Dysfunction Outcomes Rating (ODOR)
Fixed Dose
|
25.5 score on a scale (0-112)
Interval 15.0 to 34.0
|
49.9 score on a scale (0-112)
Interval 8.0 to 96.0
|
|
Olfactory Dysfunction Outcomes Rating (ODOR)
Post Taper
|
25 score on a scale (0-112)
Interval 9.0 to 35.0
|
45 score on a scale (0-112)
Interval 8.0 to 85.0
|
SECONDARY outcome
Timeframe: Baseline, after completion of eight-week fixed-dose period, and 4 weeks after completion of taper-down periodPopulation: 26 participants in placebo group completed treatment, but 25 participants completed the posttaper survey. 18 participants in the gabapentin group completed treatment, but 16 participants completed the posttaper survey.
NASAL-7 is a simple diagnostic tool for olfactory dysfunction that is based on commonly found household items and can be used by adults who suspect olfactory dysfunction. The NASAL-7 was developed by Dr. Piccirillo and colleagues in the Clinical Outcomes Research Office. The NASAL-7, contains 7 household items with each item scored as 0 for 'Cannot Smell', 1 for 'Smells Less Strong/Different Than Normal', and 2 for 'Smells Normal', for a total possible score ranging from 0-14. The following four categories of olfactory function were defined based on NASAL-7 score: anosmia (score 0-4), severe dysfunction (score 5-7), mild dysfunction (score 8-10), and normosmia (score 11-14).
Outcome measures
| Measure |
Gabapentin
n=18 Participants
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=26 Participants
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
NASAL-7
Baseline · Anosmia (0-4)
|
6 Participants
|
10 Participants
|
|
NASAL-7
Baseline · Severe dysfunction (5-7)
|
8 Participants
|
12 Participants
|
|
NASAL-7
Baseline · Mild dysfunction (8-10)
|
2 Participants
|
3 Participants
|
|
NASAL-7
Baseline · Normosmia (11-14)
|
2 Participants
|
1 Participants
|
|
NASAL-7
Fixed Dose · Anosmia (0-4)
|
4 Participants
|
7 Participants
|
|
NASAL-7
Fixed Dose · Severe dysfunction (5-7)
|
5 Participants
|
9 Participants
|
|
NASAL-7
Fixed Dose · Mild dysfunction (8-10)
|
4 Participants
|
6 Participants
|
|
NASAL-7
Fixed Dose · Normosmia (11-14)
|
5 Participants
|
4 Participants
|
|
NASAL-7
Post taper · Anosmia (0-4)
|
5 Participants
|
7 Participants
|
|
NASAL-7
Post taper · Severe dysfunction (5-7)
|
6 Participants
|
6 Participants
|
|
NASAL-7
Post taper · Mild dysfunction (8-10)
|
2 Participants
|
5 Participants
|
|
NASAL-7
Post taper · Normosmia (11-14)
|
3 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: 8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phasePopulation: 26 participants in placebo group completed treatment, but 25 participants completed the posttaper survey. 18 participants in the gabapentin group completed treatment, but 16 participants completed the posttaper survey.
CGI-Severity. The CGI-Severity scale ranges from 1 to 7, where 1 is normal function and 7 is complete anosmia. This assessment will provide subjective data on patients' baseline olfactory function prior to beginning the trial, after 8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phase
Outcome measures
| Measure |
Gabapentin
n=18 Participants
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=26 Participants
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
CGI-Severity of Smell
Assessments of the Secondary Outcome Measures of Study Groups: Baseline · Absent
|
4 Participants
|
4 Participants
|
|
CGI-Severity of Smell
Assessments of the Secondary Outcome Measures of Study Groups: Baseline · Poor
|
12 Participants
|
16 Participants
|
|
CGI-Severity of Smell
Assessments of the Secondary Outcome Measures of Study Groups: Baseline · Fair
|
1 Participants
|
4 Participants
|
|
CGI-Severity of Smell
Assessments of the Secondary Outcome Measures of Study Groups: Baseline · Good
|
1 Participants
|
1 Participants
|
|
CGI-Severity of Smell
Assessments of the Secondary Outcome Measures of Study Groups: Baseline · Very good
|
0 Participants
|
1 Participants
|
|
CGI-Severity of Smell
Assessments of the Secondary Outcome Measures of Study Groups: Baseline · Excellent
|
0 Participants
|
0 Participants
|
|
CGI-Severity of Smell
Fixed Dose · Absent
|
3 Participants
|
5 Participants
|
|
CGI-Severity of Smell
Fixed Dose · Poor
|
4 Participants
|
13 Participants
|
|
CGI-Severity of Smell
Fixed Dose · Fair
|
8 Participants
|
4 Participants
|
|
CGI-Severity of Smell
Fixed Dose · Good
|
3 Participants
|
3 Participants
|
|
CGI-Severity of Smell
Fixed Dose · Very good
|
0 Participants
|
1 Participants
|
|
CGI-Severity of Smell
Fixed Dose · Excellent
|
0 Participants
|
0 Participants
|
|
CGI-Severity of Smell
Post taper · Absent
|
2 Participants
|
3 Participants
|
|
CGI-Severity of Smell
Post taper · Poor
|
7 Participants
|
13 Participants
|
|
CGI-Severity of Smell
Post taper · Fair
|
5 Participants
|
6 Participants
|
|
CGI-Severity of Smell
Post taper · Good
|
2 Participants
|
2 Participants
|
|
CGI-Severity of Smell
Post taper · Very good
|
0 Participants
|
1 Participants
|
|
CGI-Severity of Smell
Post taper · Excellent
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 8-week Fixed-Dose period, and 4 weeks after completion of Taper-Down phasePopulation: 26 participants in placebo group completed treatment, but 25 participants completed the posttaper survey. 18 participants in the gabapentin group completed treatment, but 16 participants completed the posttaper survey.
Clinical Global Impression-Severity Scale for Parosmics (CGI-P). The CGI-P Scale is a global rating of parosmia and the single global rating ranges from 1-5, where 1 is No Distortion, 2 is Mild Distortion, 3 is Moderate Distortion, 4 is Mostly Distorted, and 5 is Complete Distortion. The response on the CGI-P will provide information on the patient's perceived severity of the distortion of their smell.
Outcome measures
| Measure |
Gabapentin
n=18 Participants
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=26 Participants
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
CGI-S of Parosmia
Assessments of Secondary Outcome Measures of Study Groups: Baseline · Complete Distortion
|
7 Participants
|
6 Participants
|
|
CGI-S of Parosmia
Assessments of Secondary Outcome Measures of Study Groups: Baseline · Mostly Distorted
|
9 Participants
|
8 Participants
|
|
CGI-S of Parosmia
Assessments of Secondary Outcome Measures of Study Groups: Baseline · Moderate Distortion
|
2 Participants
|
7 Participants
|
|
CGI-S of Parosmia
Assessments of Secondary Outcome Measures of Study Groups: Baseline · Mild Distortion
|
0 Participants
|
4 Participants
|
|
CGI-S of Parosmia
Assessments of Secondary Outcome Measures of Study Groups: Baseline · No Distortion
|
0 Participants
|
1 Participants
|
|
CGI-S of Parosmia
Fixed Dose · Complete Distortion
|
2 Participants
|
3 Participants
|
|
CGI-S of Parosmia
Fixed Dose · Mostly Distorted
|
6 Participants
|
6 Participants
|
|
CGI-S of Parosmia
Fixed Dose · Moderate Distortion
|
4 Participants
|
9 Participants
|
|
CGI-S of Parosmia
Fixed Dose · Mild Distortion
|
5 Participants
|
7 Participants
|
|
CGI-S of Parosmia
Fixed Dose · No Distortion
|
1 Participants
|
1 Participants
|
|
CGI-S of Parosmia
Post tapper · Complete Distortion
|
2 Participants
|
2 Participants
|
|
CGI-S of Parosmia
Post tapper · Mostly Distorted
|
5 Participants
|
9 Participants
|
|
CGI-S of Parosmia
Post tapper · Moderate Distortion
|
6 Participants
|
9 Participants
|
|
CGI-S of Parosmia
Post tapper · Mild Distortion
|
2 Participants
|
4 Participants
|
|
CGI-S of Parosmia
Post tapper · No Distortion
|
1 Participants
|
1 Participants
|
Adverse Events
Gabapentin
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Gabapentin
n=18 participants at risk
This arm will be given the active treatment, oral Letco (gabapentin) gelatin capsules of 300mg each.
Up to the first four weeks will be a titration period (week 1 300mg TID, week 2 600mg TID, week 3 900mg TID, week 4 1,200mg TID) as tolerated. If intolerable adverse reactions occur, the dosage will be decreased to prior tolerable dose (e.g., if 900mg TID is intolerable, dose will be decreased to 600mg TID).
The following eight weeks will be fixed dose, the highest tolerable dose from the titration period.
Up to two weeks will be a taper down tailored to the maximum dose the participant reached during the titration and fixed periods.
A maximum 14 weeks will mark the end of active treatment. Follow-up assessments will be conducted 4 weeks after completion of the taper-down period.
Gabapentin gelatin capsules 300mg: Gabapentin is an anti-epileptic also used for nerve pain. This study will investigate the efficacy of gabapentin for olfactory nerve recovery and improvement in post-Covid-19 olfactory dysfunction.
|
Placebo
n=26 participants at risk
Placebo gelatin capsules that look, smell, and taste like gabapentin capsules will be given to the placebo arm.
To preserve double-blinding of the study, subjects will receive one capsule TID the first week, the second week two capsules TID, the third week three capsules TID, and fourth week four capsules TID as tolerated. If intolerable, the dose will be decreased to prior tolerable dose.
The next eight weeks will be a fixed amount of placebo based on the highest tolerable amount from the titration period.
Subjects will then taper-down placebo to imitate the gabapentin arm for maximum two weeks based on highest dose achieved during study.
4 weeks after completion of taper-down, follow-up assessments will be conducted.
Placebo: lactose monohydrate NF
|
|---|---|---|
|
Investigations
fatigue
|
55.6%
10/18 • Number of events 18 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
42.3%
11/26 • Number of events 26 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
|
Investigations
dizziness
|
33.3%
6/18 • Number of events 18 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
0.00%
0/26 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
|
Investigations
weight gain
|
27.8%
5/18 • Number of events 18 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
0.00%
0/26 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
|
Investigations
brain fog
|
33.3%
6/18 • Number of events 18 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
7.7%
2/26 • Number of events 26 • If tolerated, all participants will complete the Titration period (≤ 4 weeks), Fixed-Dose period (8 weeks), and Taper-Down period (2 weeks) for maximum 14 weeks of active participation. In addition, there will be a 4-week, post-Taper completion follow-up for maximum total of 18-week trial duration
All reports of a Serious Adverse Event (SAE) or an Unexpected Adverse Event (UAE) will be investigated by the monitoring team and reported to Washington University HRPO according to the reporting requirements.
|
Additional Information
Jay F. Piccirillo
Washington University, Department of Otolaryngology - Head and Neck Surgery
Phone: 314-362-8641
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place