Trial Outcomes & Findings for Dose-dependent Anti-inflammatory Effects of Vitamin D in a Human Gingivitis Model (NCT NCT00779909)
NCT ID: NCT00779909
Last Updated: 2017-10-02
Results Overview
Assessment of the bleeding index will be performed on oral and buccal sites. The periodontal probe will be moved gently across the marginal gingiva of all teeth of a quadrant. After 30 seconds, absence or presence of bleeding will be scored. The number of bleeding sites is used to calculate the gingival bleeding score.
COMPLETED
EARLY_PHASE1
35 participants
end of 4 week experimental gingivitis phase
2017-10-02
Participant Flow
102 potential participants were screened for study eligibility, 61 met various exclusions criteria, and 41 were found to be eligible for randomization. Of the 41 eligible subjects 35 were randomized into the trial. The 6 not randomized were either lost to follow-up or they lost interest and withdrew their consent for further involvement.
Participant milestones
| Measure |
1- Placebo
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
vitamin D3 500 IU oral supplementation once per day for 12 weeks
|
3- Vitamin D3 2500 IU
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
9
|
8
|
8
|
|
Overall Study
COMPLETED
|
9
|
8
|
8
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
0
|
1
|
Reasons for withdrawal
| Measure |
1- Placebo
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
vitamin D3 500 IU oral supplementation once per day for 12 weeks
|
3- Vitamin D3 2500 IU
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Dose-dependent Anti-inflammatory Effects of Vitamin D in a Human Gingivitis Model
Baseline characteristics by cohort
| Measure |
1-Placebo
n=10 Participants
placebo oral supplementation once per day for 12 weeks
|
2-Vitamin D3, 500 IU
n=9 Participants
vitamin D3 500 IU oral supplementation once per day for 12 weeks
|
3-Vitamin D3, 2500 IU
n=8 Participants
vitamin D3 2500 IU oral supplementation once per day for 12 weeks
|
4-Vitamin D3, 5000 IU
n=8 Participants
vitamin D3 5000 IU oral supplementation once per day for 12 weeks
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
35 Participants
n=21 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
non-Hispanic Black
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic White
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
35 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: end of 4 week experimental gingivitis phasePopulation: Data for this outcome measure was not collected on any of the participants as it was overlooked and failure to collect these data did not come to the attention of the PI until after all follow-ups were completed.
Assessment of the bleeding index will be performed on oral and buccal sites. The periodontal probe will be moved gently across the marginal gingiva of all teeth of a quadrant. After 30 seconds, absence or presence of bleeding will be scored. The number of bleeding sites is used to calculate the gingival bleeding score.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: week 8 and week 12The Modified Gingival Index (MGI) uses non-invasive/no probing and rates mild and moderate inflammation where: 0 = absence of inflammation; 1 = mild inflammation or with slight changes in color and texture but not in all portions of gingival marginal or papillary; 2 = mild inflammation, such as the preceding criteria, in all portions of gingival marginal or papillary; 3 = moderate, bright surface inflammation, erythema, edema and/or hypertrophy of gingival marginal or papillary; 4 = severe inflammation: erythema, edema and/or marginal gingival hypertrophy of the unit or spontaneous bleeding, papillary, congestion or ulceration. The MGI can be obtained by adding the values of each tooth and dividing by the number of teeth examined. The MGI may be scored for all surfaces of all or selected teeth or for selected areas of all or selected teeth. A score from 0.1-1.0 = mild inflammation; 1.1-2.0 = moderate inflammation from, and 2.1-3.0 signifies severe inflammation.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Mandibular Modified Gingival Index (MGI) Score
8wk mandibular MGI score
|
1.83 units on a scale
Standard Deviation 0.27
|
1.76 units on a scale
Standard Deviation 0.46
|
1.62 units on a scale
Standard Deviation 0.44
|
1.67 units on a scale
Standard Deviation 0.28
|
|
Mandibular Modified Gingival Index (MGI) Score
12wk mandibular MGI score
|
2.12 units on a scale
Standard Deviation 0.14
|
1.97 units on a scale
Standard Deviation 0.24
|
2.02 units on a scale
Standard Deviation 0.20
|
2.19 units on a scale
Standard Deviation 0.15
|
PRIMARY outcome
Timeframe: week 8 and week 12The Modified Gingival Index (MGI) uses non-invasive/no probing and rates mild and moderate inflammation where: 0 = absence of inflammation; 1 = mild inflammation or with slight changes in color and texture but not in all portions of gingival marginal or papillary; 2 = mild inflammation, such as the preceding criteria, in all portions of gingival marginal or papillary; 3 = moderate, bright surface inflammation, erythema, edema and/or hypertrophy of gingival marginal or papillary; 4 = severe inflammation: erythema, edema and/or marginal gingival hypertrophy of the unit or spontaneous bleeding, papillary, congestion or ulceration. The MGI can be obtained by adding the values of each tooth and dividing by the number of teeth examined. The MGI may be scored for all surfaces of all or selected teeth or for selected areas of all or selected teeth. A score from 0.1-1.0 = mild inflammation; 1.1-2.0 = moderate inflammation from, and 2.1-3.0 signifies severe inflammation.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Maxillary Modified Gingival Index (MGI) Score
8wk maxillary MGI score
|
1.78 units on a scale
Standard Deviation 0.29
|
1.63 units on a scale
Standard Deviation 0.40
|
1.57 units on a scale
Standard Deviation 0.39
|
1.61 units on a scale
Standard Deviation 0.31
|
|
Maxillary Modified Gingival Index (MGI) Score
12wk maxillary MGI score
|
2.11 units on a scale
Standard Deviation 0.16
|
1.87 units on a scale
Standard Deviation 0.30
|
1.9 units on a scale
Standard Deviation 0.30
|
2.1 units on a scale
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: week 8 and week 12The Turesky plaque index was used. In this index, plaque is identified using a disclosing solution and scored using a 0 to 5 scale in which a score of 0= No plaque, 1= Separate flecks of plaque, 2= continuous band of plaque less or equal 1 mm, 3= Continuous band of plaque greater than 1 mm but less than 1/3 of crown height, 4= Continuous band of plaque greater or equal 1/3 but less or equal 2/3 of crown height, and 5= Continuous band of plaque greater 2/3 of crown height. Each tooth receives 6 individual scores at: mesial, middle, and distal scores for both the facial and lingual surfaces. An individual's score is derived by adding the scores at each site and dividing by the number of sites evaluated. Higher scores denote higher plaque accumulation. Lower scores are more favorable.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Mandibular Plaque Index (PI) Score
8wk mandibular PI score
|
1.84 units on a scale
Standard Deviation 0.60
|
1.77 units on a scale
Standard Deviation 0.44
|
1.82 units on a scale
Standard Deviation 0.46
|
1.82 units on a scale
Standard Deviation 0.57
|
|
Mandibular Plaque Index (PI) Score
12wk mandibular PI score
|
2.92 units on a scale
Standard Deviation 0.71
|
2.93 units on a scale
Standard Deviation 0.50
|
2.74 units on a scale
Standard Deviation 0.52
|
2.89 units on a scale
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: week 8 and week 12The Turesky plaque index was used. In this index, plaque is identified using a disclosing solution and scored using a 0 to 5 scale in which a score of 0= No plaque, 1= Separate flecks of plaque, 2= continuous band of plaque less or equal 1 mm, 3= Continuous band of plaque greater than 1 mm but less than 1/3 of crown height, 4= Continuous band of plaque greater or equal 1/3 but less or equal 2/3 of crown height, and 5= Continuous band of plaque greater 2/3 of crown height. Each tooth receives 6 individual scores at: mesial, middle, and distal scores for both the facial and lingual surfaces. An individual's score is derived by adding the scores at each site and dividing by the number of sites evaluated. Higher scores denote higher plaque accumulation. Lower scores are more favorable.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Maxillary Plaque Index (PI) Score
8wk maxillary PI score
|
1.56 units on a scale
Standard Deviation 0.55
|
1.71 units on a scale
Standard Deviation 0.44
|
1.69 units on a scale
Standard Deviation 0.49
|
1.68 units on a scale
Standard Deviation 0.56
|
|
Maxillary Plaque Index (PI) Score
12 wk maxillary PI score
|
2.77 units on a scale
Standard Deviation 0.42
|
3 units on a scale
Standard Deviation 0.32
|
2.81 units on a scale
Standard Deviation 0.32
|
2.89 units on a scale
Standard Deviation 0.47
|
SECONDARY outcome
Timeframe: week 8 and week 12GCF will be collected by placing a filter paper strip at the opening of the gingival crevice. After carefully removing the supragingival plaque from the sampling area, a paper strip will be placed for 30s or until visibly wet. Sampling time will be recorded and GCF volume collected with each sample will be quantified using a Periotron device. GCF volume will be sampled from three mesial sites per subject: The upper left central incisor, the first upper left premolar and the first upper left molar. Should any of these teeth be missing, substitution will occur in the following order (i) the contralateral tooth, (ii) the distally adjacent tooth, or (iii) the distally adjacent tooth of the contralateral tooth. Should a sample be visibly contaminated with blood, the sample will be discarded and substitution will occur as described above.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Gingival Crevicular Fluid (GCF) Volume
8wk GCF volume site 3
|
70.4 ul
Standard Deviation 32.9
|
92.9 ul
Standard Deviation 26.0
|
58.4 ul
Standard Deviation 19.7
|
59.9 ul
Standard Deviation 16.5
|
|
Gingival Crevicular Fluid (GCF) Volume
12wk GCF volume site 3
|
95.9 ul
Standard Deviation 27.4
|
99.1 ul
Standard Deviation 37.7
|
64.8 ul
Standard Deviation 20.0
|
92 ul
Standard Deviation 39.7
|
|
Gingival Crevicular Fluid (GCF) Volume
8wk GCF volume site 1
|
38.1 ul
Standard Deviation 12.5
|
49.1 ul
Standard Deviation 21.3
|
37.1 ul
Standard Deviation 10.0
|
57.6 ul
Standard Deviation 24.2
|
|
Gingival Crevicular Fluid (GCF) Volume
12wk GCF volume site 1
|
50.8 ul
Standard Deviation 13.1
|
66.5 ul
Standard Deviation 31.8
|
35.1 ul
Standard Deviation 7.8
|
55.9 ul
Standard Deviation 48.0
|
|
Gingival Crevicular Fluid (GCF) Volume
8wk GCF volume site 2
|
53.7 ul
Standard Deviation 9.8
|
53.5 ul
Standard Deviation 23.4
|
42.5 ul
Standard Deviation 27.4
|
61.0 ul
Standard Deviation 36.0
|
|
Gingival Crevicular Fluid (GCF) Volume
12wk GCF volume site 2
|
83.6 ul
Standard Deviation 24.5
|
71.9 ul
Standard Deviation 29.5
|
54.3 ul
Standard Deviation 24.6
|
72.4 ul
Standard Deviation 39.6
|
SECONDARY outcome
Timeframe: week 8 and week 12GCF will be collected by placing a filter paper strip at the opening of the gingival crevice. After carefully removing the supragingival plaque from the sampling area, a paper strip will be placed for 30s or until visibly wet. Sampling time will be recorded and GCF volume collected with each sample will be quantified using a Periotron device. GCF volume will be sampled from three mesial sites per subject: The upper left central incisor, the first upper left premolar and the first upper left molar. Should any of these teeth be missing, substitution will occur in the following order (i) the contralateral tooth, (ii) the distally adjacent tooth, or (iii) the distally adjacent tooth of the contralateral tooth. Should a sample be visibly contaminated with blood, the sample will be discarded and substitution will occur as described above. Concentrations of TNF-alpha, IL-1 beta, IL-2, and IL-12 will be measured and means and SDs will be calculated for each study arm.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
8wk TNF-alpha
|
0.97 pg/site
Standard Deviation 1.14
|
1.53 pg/site
Standard Deviation 1.86
|
1.34 pg/site
Standard Deviation 1.93
|
1.87 pg/site
Standard Deviation 3.14
|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
12wk TNF-alpha
|
1.00 pg/site
Standard Deviation 1.04
|
1.11 pg/site
Standard Deviation 1.32
|
1.73 pg/site
Standard Deviation 3.02
|
7.94 pg/site
Standard Deviation 18.12
|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
8wk IL-1 beta
|
0.04 pg/site
Standard Deviation 0.00
|
0.05 pg/site
Standard Deviation 0.02
|
0.04 pg/site
Standard Deviation 0.00
|
0.04 pg/site
Standard Deviation 0.00
|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
12wk IL-1 beta
|
0.04 pg/site
Standard Deviation 0.00
|
0.04 pg/site
Standard Deviation 0.02
|
0.04 pg/site
Standard Deviation 0.00
|
0.04 pg/site
Standard Deviation 0.00
|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
8wk IL-2
|
24.11 pg/site
Standard Deviation 34.83
|
13.44 pg/site
Standard Deviation 2.66
|
13.13 pg/site
Standard Deviation 6.52
|
13.07 pg/site
Standard Deviation 6.71
|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
12wk IL-2
|
20.78 pg/site
Standard Deviation 17.31
|
12.5 pg/site
Standard Deviation 0.00
|
12.56 pg/site
Standard Deviation 0.18
|
13.36 pg/site
Standard Deviation 1.70
|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
8wk IL-12
|
0.65 pg/site
Standard Deviation 1.22
|
0.11 pg/site
Standard Deviation 0.17
|
0.03 pg/site
Standard Deviation 0.04
|
0.96 pg/site
Standard Deviation 2.10
|
|
Gingival Crevicular Fluid (GCF) Concentrations of TNF-alpha, IL1-beta, IL-2, IL-12
12wk IL-12
|
0.62 pg/site
Standard Deviation 1.10
|
0.06 pg/site
Standard Deviation 0.07
|
0.02 pg/site
Standard Deviation 0.01
|
1.08 pg/site
Standard Deviation 2.28
|
SECONDARY outcome
Timeframe: week 7, week 12The serum calcium blood test measures the total calcium in the participants' blood. The normal range for total serum calcium concentration in adults is 8.9-10.2 mg/dL.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Serum Calcium
7wk serum calcium
|
9.6 mg/dl
Standard Deviation 0.4
|
9.1 mg/dl
Standard Deviation 0.3
|
9.2 mg/dl
Standard Deviation 0.3
|
9.1 mg/dl
Standard Deviation 0.5
|
|
Serum Calcium
12wk serum calcium
|
9.4 mg/dl
Standard Deviation 0.4
|
9.2 mg/dl
Standard Deviation 0.5
|
9.2 mg/dl
Standard Deviation 0.3
|
9.3 mg/dl
Standard Deviation 0.2
|
SECONDARY outcome
Timeframe: week 4, week 7, week 12Urinary calcium ratios were calculated from urine samples at week 4, 7, and 12. A normal reference interval for the urine calcium (mg/dL):urine creatinine (mg/dL) ratio is \<0.14.
Outcome measures
| Measure |
1- Placebo
n=9 Participants
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
3.Vitamin D3, 2500 IU
n=8 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 Participants
vitamin D3: oral supplementation once per day for 12 weeks
|
|---|---|---|---|---|
|
Urinary Calcium/Creatinine Ratio
4wk calcium/creatinine ratio
|
0.07 ratio
Standard Deviation 0.1
|
0.06 ratio
Standard Deviation 0.03
|
0.07 ratio
Standard Deviation 0.04
|
0.09 ratio
Standard Deviation 0.01
|
|
Urinary Calcium/Creatinine Ratio
7wk calcium/creatinine ratio
|
0.09 ratio
Standard Deviation 0.1
|
0.07 ratio
Standard Deviation 0.04
|
0.09 ratio
Standard Deviation 0.02
|
0.13 ratio
Standard Deviation 0.13
|
|
Urinary Calcium/Creatinine Ratio
12wk calcium/creatinine ratio
|
0.12 ratio
Standard Deviation 0.1
|
0.07 ratio
Standard Deviation 0.03
|
0.11 ratio
Standard Deviation 0.09
|
0.11 ratio
Standard Deviation 0.07
|
Adverse Events
1- Placebo
2- Vitamin D3, 500 IU
3- Vitamin D3 2500 IU
4- Vitamin D3 5000 IU
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
1- Placebo
n=9 participants at risk
placebo oral supplementation once per day for 12 weeks
|
2- Vitamin D3, 500 IU
n=8 participants at risk
vitamin D3, 500 IU capsule once per day for 12 weeks
|
3- Vitamin D3 2500 IU
n=8 participants at risk
vitamin D3, 2500 IU capsule once per day for 12 weeks
|
4- Vitamin D3 5000 IU
n=7 participants at risk
vitamin D3, 5000 IU capsule once per day for 12 weeks
|
|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
0.00%
0/9
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/7
|
Additional Information
Raul I Garcia, DMD
Boston University School of Dental Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place