Effect of Topical Sulforaphane on Skin Fragility Seen in Skin Aging and With Ultraviolet Exposure

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03126539
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study aims to compare the expression of keratins before and after application of sulforaphane (SF) to determine whether this agent alters skin fragility seen in both intrinsic and extrinsic skin aging and UV light exposure.

Condition or Disease	Intervention/Treatment	Phase
Aging	Drug: Sulforaphane; Radiation: Narrow-band Ultraviolet B exposure; Procedure: 4 mm skin punch biopsy	Phase 2

Detailed Description

The primary purpose of the study is to compare the expression of keratins before and after application of sulforaphane (SF) and determine whether these findings alter skin fragility seen in both intrinsic and extrinsic skin aging as well as in ultraviolet (UV) light exposure.

This investigation will be done in collaboration with researchers from the Department of Biochemistry and Molecular Biology and Bloomberg School of Public Health at Johns Hopkins University. The study population recruited by Johns Hopkins Department of Dermatology will include up to 50 individuals over the age of 18 with healthy skin. Each study participant will have four on-site study visits and will be asked to contribute photographs, undergo non invasive elasticity measurements, use topical sulforaphane for 7 days and contribute up to four biopsy specimens for laboratory study. The investigators will also evaluate any differences in keratins' expression in skin exposed to acute UV light, separately and after pretreatment with sulforaphane.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Effect of Topical Sulforaphane on Skin Fragility Seen in Skin Aging and With Ultraviolet Exposure
• Actual Study Start Date: Sep 15, 2017
• Actual Primary Completion Date: Jan 25, 2019
• Actual Study Completion Date: Jan 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Sulforaphane will be applied topically to both sites for up to 7 consecutive nights. Biopsies will be obtained prior to, and immediately after this intervention, on standard photoprotected and photoexposed sites.	Drug: Sulforaphane; Isothiocyanate sulforaphane (SF), derived from broccoli sprouts, has been known to induce an antioxidant response through the Keap1-Nrf2-antioxidant response element pathway.; Other Names: Broccoli sprout extract; isothiocyanate sulforaphane ; Procedure: 4 mm skin punch biopsy; All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.; Other Names: biopsy
Experimental: Group B Two photoprotected sites will be identified. Sulforaphane will be applied topically to a single selected site for up to 7 consecutive nights. Both site will be exposed to UV. Biopsies of both sites will be obtained prior to, and 24 hours after UV exposure.	Drug: Sulforaphane; Isothiocyanate sulforaphane (SF), derived from broccoli sprouts, has been known to induce an antioxidant response through the Keap1-Nrf2-antioxidant response element pathway.; Other Names: Broccoli sprout extract; isothiocyanate sulforaphane ; Radiation: Narrow-band Ultraviolet B exposure; The investigators will use a Lumera ultraviolet B (UVB) light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320 nm).; Other Names: UVB, UV ; Procedure: 4 mm skin punch biopsy; All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.; Other Names: biopsy

Outcome Measures

Primary Outcome Measures

1. Clinical Change Score for Mottled Hyperpigmentation [Clinical Change Score for Mottled Hyperpigmentation , up to 1 week]

   Clinical assessment of mottled hyperpigmentation pre and post Sulforaphane (SF) treatment will be done for both photoprotected and photodamaged skin treated with sulforaphane. Mottled Hyperpigmentation Score system will be applied, with scale of 0 to 4, 4= clear improvement after 1 week of SF or placebo application.

Secondary Outcome Measures

1. Gene Expression Changes as Assessed by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) [Up to 6 months]

   We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using RT-PCR.

2. Gene Expression Changes as Assessed by Immunohistochemistry (IHC) [Up to 6 months]

   We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using IHC.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Participants must be over the age of 18 years old with healthy skin;

2. Must be healthy enough to undergo skin biopsy, UV light irradiation, and other study procedures in the opinion of the investigator;

3. Must be willing to comply with the requirements of the protocol;

4. Must have the ability to understand and communicate with the investigator;

5. Participant must provide informed consent.

Exclusion Criteria:

1. Subjects who are unable to provide informed consent;

2. Subject with significant medical history or current skin diseases that the investigator feels is not safe for study participation;

3. Subjects who have been treated with systemic retinoids or steroids within the past month prior to entry to the study;

4. Subjects who have been treated with topical steroids, retinoids or other topical drugs used within 2 weeks prior to entry to the study;

5. Recently treated or current skin diseases that would affect clinical evaluation and biopsy;

6. Subjects with a known allergy to broccoli.

7. Presence or suspicion of bleeding disorder or diathesis which would complicate biopsy.

8. Subjects with a history of excessive scar or keloid formation in the past 10 years.

9. Pregnant or nursing subjects (self-reported).

10. Subjects with known allergy to anesthetics used.

11. Patients with history of investigational drug use in the 30 days prior to entry into the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cutaneous Translational Research Program, Department of Dermatology, Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University

Investigators

• Principal Investigator: Anna Chien, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 16, 2017

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03126539
• Other Study ID Numbers: IRB00105668
• First Posted: Apr 24, 2017
• Last Update Posted: Jun 30, 2022
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Johns Hopkins University: aging; ultraviolet exposure; skin fragility; sulforaphane
• Additional relevant MeSH terms: Sulforaphane

Study Results

Participant Flow

Arm/Group Title	Group A: No UV Exposure - Sulforaphane	Group A: No UV Exposure - Placebo	Group A: No UV Exposure - No Treatment Control	Group B With UV Exposure - Sulforaphane	Group B With UV Exposure - Placebo
Arm/Group Description	One photoexposed site will be identified. 500nmol Sulforaphane in jojoba oil will be applied topically to site every night for up to 7 consecutive nights. Biopsy will be obtained after this intervention on standard photoexposed site. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than five total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	One photoexposed site will be identified. Jojoba oil will be applied topically to site every night for up to 7 consecutive nights. Biopsy will be obtained after this intervention on standard photoexposed site. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than five total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	One photoprotected site and two photoexposed sites will be identified. No treatment will be administered at this site. A 4mm punch biopsy will be obtained from this site as a control. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than five total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	One photoprotected site will be identified. 500nmol sulforaphane in jojoba oil will be applied topically to the site for up to 7 consecutive nights. Site will be exposed to UV. Biopsy of site will be obtained prior to, and 24 hours after UV exposure. Narrow-band Ultraviolet B (UVB) exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and typically heals well without complications.	One photoprotected sites will be identified. Jojoba Oil will be applied topically to a single selected site for up to 7 consecutive nights. Site will be exposed to UV. Biopsies of site will be obtained prior to, and 24 hours after UV exposure. Narrow-band Ultraviolet B (UVB) exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications.
Period Title: Overall Study
STARTED	9	9	9	0	0
COMPLETED	8	8	8	0	0
NOT COMPLETED	1	1	1	0	0

Baseline Characteristics

Arm/Group Title	Group A: No UV Exposure	Group B With UV Exposure	Total
Arm/Group Description	Two photoprotected sites will be identified. Sulforaphane will be applied topically to both sites for up to 7 consecutive nights. Biopsies will be obtained prior to, and immediately after this intervention, on standard photoprotected and photoexposed sites. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	Two photoprotected sites will be identified. Sulforaphane will be applied topically to a single selected site for up to 7 consecutive nights. Both site will be exposed to UV. Biopsies of both sites will be obtained prior to, and 24 hours after UV exposure. Narrow-band Ultraviolet B exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320 nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications	Total of all reporting groups
Overall Participants	9	0	9
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57	57
Sex: Female, Male (Count of Participants)
Female	7 77.8%	7 Infinity
Male	2 22.2%	2 Infinity
Race/Ethnicity, Customized (Count of Participants)
Caucasian	9 100%	9 Infinity
Region of Enrollment (Count of Participants)
United States	9 100%	9 Infinity

Outcome Measures

1. Primary Outcome

Title	Clinical Change Score for Mottled Hyperpigmentation
Description	Clinical assessment of mottled hyperpigmentation pre and post Sulforaphane (SF) treatment will be done for both photoprotected and photodamaged skin treated with sulforaphane. Mottled Hyperpigmentation Score system will be applied, with scale of 0 to 4, 4= clear improvement after 1 week of SF or placebo application.
Time Frame	Clinical Change Score for Mottled Hyperpigmentation , up to 1 week

Outcome Measure Data

Analysis Population Description

We did not enroll any participant in group B. The results we got were not the comparison between no UV exposure group and UV exposure. Instead, the results were the clinical change score between the SF treated skin spots and no SF treated (placebo) skin spots of each participant.

Arm/Group Title	Group A: No UV Exposure - Sulforaphane	Group A: No UV Exposure - Placebo	Group A: No UV Exposure - No Treatment Control	Group B With UV Exposure - Sulforaphane	Group B With UV Exposure - Placebo
Arm/Group Description	One photoexposed site will be identified. 500nmol Sulforaphane in jojoba oil will be applied topically to site every night for up to 7 consecutive nights. Biopsy will be obtained after this intervention on standard photoexposed site. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than five total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	One photoexposed site will be identified. Jojoba oil will be applied topically to site every night for up to 7 consecutive nights. Biopsy will be obtained after this intervention on standard photoexposed site. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than five total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	One photoprotected site and two photoexposed sites will be identified. No treatment will be administered at this site. A 4mm punch biopsy will be obtained from this site as a control. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than five total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	One photoprotected site will be identified. 500nmol sulforaphane in jojoba oil will be applied topically to the site for up to 7 consecutive nights. Site will be exposed to UV. Biopsy of site will be obtained prior to, and 24 hours after UV exposure. Narrow-band Ultraviolet B (UVB) exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and typically heals well without complications.	One photoprotected sites will be identified. Jojoba Oil will be applied topically to a single selected site for up to 7 consecutive nights. Site will be exposed to UV. Biopsies of site will be obtained prior to, and 24 hours after UV exposure. Narrow-band Ultraviolet B (UVB) exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications.
Measure Participants	8	8	9	0	0
Measure Skin spots	8	8	24	0	0
Mean (Standard Error) [score on a scale]	2.8 (0.4)	.94 (.2)	0 (0)

2. Secondary Outcome

Title	Gene Expression Changes as Assessed by Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR)
Description	We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using RT-PCR.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected.

Arm/Group Title	Group A: No UV Exposure	Group B With UV Exposure
Arm/Group Description	Two photoprotected sites will be identified. Sulforaphane will be applied topically to both sites for up to 7 consecutive nights. Biopsies will be obtained prior to, and immediately after this intervention, on standard photoprotected and photoexposed sites. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	Two photoprotected sites will be identified. Sulforaphane will be applied topically to a single selected site for up to 7 consecutive nights. Both site will be exposed to UV. Biopsies of both sites will be obtained prior to, and 24 hours after UV exposure. Narrow-band Ultraviolet B exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320 nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications
Measure Participants	0	0

3. Secondary Outcome

Title	Gene Expression Changes as Assessed by Immunohistochemistry (IHC)
Description	We will measure the fold-change in gene expression in human skin after acute UV light exposure, separately and in combination with application of topical sulforaphane using IHC.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected.

Arm/Group Title	Group A	Group B
Arm/Group Description	Sulforaphane will be applied topically to both sites for up to 7 consecutive nights. Biopsies will be obtained prior to, and immediately after this intervention, on standard photoprotected and photoexposed sites. Sulforaphane: Isothiocyanate sulforaphane (SF), derived from broccoli sprouts, has been known to induce an antioxidant response through the Keap1-Nrf2-antioxidant response element pathway. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.	Two photoprotected sites will be identified. Sulforaphane will be applied topically to a single selected site for up to 7 consecutive nights. Both site will be exposed to UV. Biopsies of both sites will be obtained prior to, and 24 hours after UV exposure. Sulforaphane: Isothiocyanate sulforaphane (SF), derived from broccoli sprouts, has been known to induce an antioxidant response through the Keap1-Nrf2-antioxidant response element pathway. Narrow-band Ultraviolet B exposure: The investigators will use a Lumera ultraviolet B (UVB) light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320 nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the c
Measure Participants	0	0

Adverse Events

Time Frame	Four weeks
Adverse Event Reporting Description	We did not enroll any participants in group B.
Arm/Group Title	Group A: No UV Exposure		Group B With UV Exposure
Arm/Group Description	Two photoprotected sites will be identified. Sulforaphane will be applied topically to both sites for up to 7 consecutive nights. Biopsies will be obtained prior to, and immediately after this intervention, on standard photoprotected and photoexposed sites. 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications and blends well with the surrounding skin.		Two photoprotected sites will be identified. Sulforaphane will be applied topically to a single selected site for up to 7 consecutive nights. Both site will be exposed to UV. Biopsies of both sites will be obtained prior to, and 24 hours after UV exposure. Narrow-band Ultraviolet B exposure: The investigators will use a Lumera UVB light phototherapy device which allows for targeted delivery of controlled doses of UVB radiation (emission spectrum 290-320 nm). 4 mm skin punch biopsy: All areas will be biopsied using standard punch biopsy tools and following standard clinical protocols, including cleansing the skin with an alcohol wipe and injecting local anesthesia with lidocaine and epinephrine. No more than four total skin biopsies will be obtained from a volunteer over the course of the study. After removal of the tissue sample, one or two sutures are placed to close the circular opening. Sutures are removed and a scar is formed, but typically heals well without complications
All Cause Mortality
	Group A: No UV Exposure		Group B With UV Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/0 (NaN)
Serious Adverse Events
	Group A: No UV Exposure		Group B With UV Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Group A: No UV Exposure		Group B With UV Exposure
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.