Trial Outcomes & Findings for Dysport for the Treatment of OMD (NCT NCT01921270)

NCT ID: NCT01921270

Last Updated: 2017-11-17

Results Overview

This scale measures the severity of dystonia for the jaw and tongue by a blinded rater. Dystonia is rated from 0 to 10: 0=No dystonia present, 1=Minimal dystonia, 5=Moderate dystonia,10=Most severe dystonia

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Baseline, Week 6, Week 12

Results posted on

2017-11-17

Participant Flow

Participant milestones

Participant milestones
Measure
Dysport Injections
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Overall Study
STARTED
18
Overall Study
COMPLETED
17
Overall Study
NOT COMPLETED
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Dysport Injections
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Overall Study
Withdrawal by Subject
1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Age, Continuous
62.83 years
STANDARD_DEVIATION 10.45 • n=18 Participants
Sex: Female, Male
Female
12 Participants
n=18 Participants
Sex: Female, Male
Male
6 Participants
n=18 Participants
Region of Enrollment
United States
18 Participants
n=18 Participants

PRIMARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

This scale measures the severity of dystonia for the jaw and tongue by a blinded rater. Dystonia is rated from 0 to 10: 0=No dystonia present, 1=Minimal dystonia, 5=Moderate dystonia,10=Most severe dystonia

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater
Baseline
3.80 units on a scale
Standard Deviation 2.29
Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater
Week 6
3.57 units on a scale
Standard Deviation 2.05
Mean Global Dystonia Rating Scale Score as Measured by Blinded Rater
Week 12
3.71 units on a scale
Standard Deviation 2.18

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Data were not collected.

Measure of jaw pain by visual analogue scale (0-100) where 0 represents "no pain" and 100 represents the "most severe pain".

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The SCS-PD measures drooling. Individual items are scored on a scale from 0-3 where 0 represents "never" and 3 represents "always". The overall maximum score is 21. A higher score indicates greater drooling severity. A lower score indicates lesser severity.

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score
Baseline
3.00 units on a scale
Standard Deviation 3.91
Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score
Week 6
2.72 units on a scale
Standard Deviation 4.28
Mean Sialorrhea Clinical Scale for Parkinson's Disease (SCS-PD) Score
Week 12
2.53 units on a scale
Standard Deviation 3.20

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: Data were not collected.

The patient will be asked to estimate how many times they tend to accidentally/involuntarily bite their tongue per day.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

Ease of chewing and swallowing will be assessed by the SDQ-20 (modified to exclude question 5 due to redundancy as it relates to drooling and question 15 which is not relevant to the study as it involves prior aspiration pneumonias). Individual items are scored from 0 (never) to 3 (very frequently). The overall score is the total for all items; a higher score indicating more frequent swallowing disturbance; a lower score indicating no or less frequent disturbance, with a possible maximum score of 39.

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Swallowing Disturbance Questionnaire (SDQ-20) Score
Baseline
13.17 units on a scale
Standard Deviation 9.51
Mean Swallowing Disturbance Questionnaire (SDQ-20) Score
Week 6
15.61 units on a scale
Standard Deviation 8.56
Mean Swallowing Disturbance Questionnaire (SDQ-20) Score
Week 12
13.29 units on a scale
Standard Deviation 8.54

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The Fahn-Marsden Part B "Speech" Question assesses the ease of producing speech. Responses range from 0=Normal, 1=Slightly involved, easily understood, 2=Some difficulty understanding, 3=Marked difficulty understanding.

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Fahn-Marsden Part B "Speech" Question (BFM-q21) Rating
Baseline
1.33 units on a scale
Standard Deviation .91
Mean Fahn-Marsden Part B "Speech" Question (BFM-q21) Rating
Week 6
.94 units on a scale
Standard Deviation .87
Mean Fahn-Marsden Part B "Speech" Question (BFM-q21) Rating
Week 12
.94 units on a scale
Standard Deviation .75

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The OMDQ-25 is a subjective quality of life measurement made for patients with Oromandibular Dystonia. The maximum total score is 100 indicating the highest quality of life. A score of 50 indicates a mediocre quality of life. A lower score indicates perceived lower quality of life.

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score
Baseline
47.39 units on a scale
Standard Deviation 23.00
Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score
Week 6
43.22 units on a scale
Standard Deviation 23.24
Mean Oromandibular Dystonia Quality of Life Questionnaire (OMDQ-25) Score
Week 12
38.00 units on a scale
Standard Deviation 21.42

SECONDARY outcome

Timeframe: Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. Responses are scored on a scale from 1 to 7; 1 represents "very much improved" and 7 represents "very much worse".

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Global Clinical Impression - Improvement Scale (CGI) Index Score
Week 6
2.89 units on a scale
Standard Deviation 1.28
Mean Global Clinical Impression - Improvement Scale (CGI) Index Score
Week 12
2.53 units on a scale
Standard Deviation .87

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Responses are scored on a scale from 1 to 7; 1 represents "normal, not at all ill" and 7 represents "among the most extremely ill patients".

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score
Baseline
4.06 units on a scale
Standard Error 1.00
Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score
Week 6
3.22 units on a scale
Standard Error 1.11
Mean Global Clinical Impression Scale (CGI-S) With Severity Index Score
Week 12
3.29 units on a scale
Standard Error .92

SECONDARY outcome

Timeframe: Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The Clinical Global Impression - Efficacy Index is a 4×4 rating scale that assesses the therapeutic effect of treatment. Responses range on a scale from 0 to 4 with 4 being the best response.

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Global Clinical Impression- Efficacy Index Score
Week 6
1.51 units on a scale
Standard Deviation .93
Mean Global Clinical Impression- Efficacy Index Score
Week 12
1.93 units on a scale
Standard Deviation .97

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The UDRS measures dystonia severity. The UDRS is being rated by un-blinded video evaluators regarding severity of subject's dystonia. Scores range from 0 to 10; 0 indicating no dystonia, 5 indicating moderate dystonia, and 10 indicating the worst dystonia.

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater
Baseline
4.67 units on a scale
Standard Deviation 1.15
Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater
Week 6
3.47 units on a scale
Standard Deviation 1.58
Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Un-blinded Rater
Week 12
3.26 units on a scale
Standard Deviation 1.47

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

This scale measures the severity of dystonia for the jaw and tongue by an un-blinded rater. Dystonia is rated from 0 to 10: 0=No dystonia present, 1=Minimal dystonia, 5=Moderate dystonia,10=Most severe dystonia

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater
Baseline
5.67 units on a scale
Standard Deviation 1.53
Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater
Week 6
3.94 units on a scale
Standard Deviation 2.10
Mean Global Dystonia Rating Scale Score as Measured by Un-blinded Rater
Week 12
3.76 units on a scale
Standard Deviation 2.25

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12

Population: Participants who received low dose Dysport injections and completed all study visits. Two participants received two injections each for which data from the second were included in the analysis. For change from baseline to week 6, 18 subjects analyzed, for change from baseline to week 12, 17 subjects analyzed as one subject dropped out at 6 weeks.

The UDRS measures dystonia severity. The UDRS is being rated by blinded video evaluators regarding severity of subject's dystonia. Scores range from 0 to 10; 0 indicating no dystonia, 5 indicating moderate dystonia, and 10 indicating the worst dystonia.

Outcome measures

Outcome measures
Measure
Dysport Injections
n=18 Participants
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater
Baseline
3.50 units on a scale
Standard Deviation 1.92
Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater
Week 6
3.47 units on a scale
Standard Deviation 1.79
Mean Unified Dystonia Rating Scale (UDRS) Score as Measured by Blinded Rater
Week 12
3.30 units on a scale
Standard Deviation 1.72

Adverse Events

Dysport Injections

Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Dysport Injections
n=18 participants at risk
Participants with OMD who have been previously treated with any botulinum toxin Type A were injected with Dysport®. Low Dose - AbobotulinumtoxinA: Participants will receive low dose AbobotulinumtoxinA injections. Location of injections will be determined by the clinician to treat the individual's dystonic symptom. Muscles that may be included for in injection for OMD with Jaw Closing: Medial Pterygoid 50 units, Masseter 25 units Muscles that may be included in injection for OMD with Jaw Opening: Lateral Pterygoid 50 units, Anterior digastrics 10 units Muscle that will be included in injection for OMD with Tongue Protrusion: Genioglossus 7.5 units
Gastrointestinal disorders
Dysphagia
33.3%
6/18 • Number of events 6 • Adverse events were collected throughout the duration of the study (4 years).
Nervous system disorders
Change in Speech
27.8%
5/18 • Number of events 5 • Adverse events were collected throughout the duration of the study (4 years).
Nervous system disorders
Soft Palate Weakness
22.2%
4/18 • Number of events 4 • Adverse events were collected throughout the duration of the study (4 years).
Metabolism and nutrition disorders
Xerostomia
22.2%
4/18 • Number of events 4 • Adverse events were collected throughout the duration of the study (4 years).
Gastrointestinal disorders
Throat Tightness/Congestion
16.7%
3/18 • Number of events 3 • Adverse events were collected throughout the duration of the study (4 years).
Metabolism and nutrition disorders
Drooling
16.7%
3/18 • Number of events 3 • Adverse events were collected throughout the duration of the study (4 years).
Metabolism and nutrition disorders
Difficulty Chewing
11.1%
2/18 • Number of events 2 • Adverse events were collected throughout the duration of the study (4 years).
Metabolism and nutrition disorders
Food Falling Out of Mouth
11.1%
2/18 • Number of events 2 • Adverse events were collected throughout the duration of the study (4 years).
Respiratory, thoracic and mediastinal disorders
Coughing
11.1%
2/18 • Number of events 2 • Adverse events were collected throughout the duration of the study (4 years).
Investigations
Weight Loss
11.1%
2/18 • Number of events 2 • Adverse events were collected throughout the duration of the study (4 years).
General disorders
Flu-like Symptoms
11.1%
2/18 • Number of events 2 • Adverse events were collected throughout the duration of the study (4 years).
Nervous system disorders
Headache
11.1%
2/18 • Number of events 2 • Adverse events were collected throughout the duration of the study (4 years).

Additional Information

Dr. Stewart Factor

Emory University

Phone: 404-728-4952

Results disclosure agreements

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