Ultraviolet RaysPhase 1NCT01978483
Effect of RANKL Inhibition on UV-induced Immunosuppression
A Phase 1 study testing Denosumab, UVB exposure and Diphenylcyclopropenone in people with Ultraviolet Rays and Immunosuppression, run by Innovaderm Research Inc. at 1 site in Canada.
Trial summary
Ultraviolet (UV) light is part of normal sunlight and has many effects on human skin and health. One of the harmful effects of long-term UV light exposure is that it can cause skin cancer. The mechanism by which UV light causes skin cancer is not entirely understood. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ultraviolet Rays, Immunosuppression, Hypersensitivity, Delayed
- What is being tested?
- Denosumab, UVB exposure and Diphenylcyclopropenone
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2013to Jun 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 1. Men or postmenopausal women 18 years of age or older at time of consent.
- 2. Male subject or his female partner (this criterion does not apply to post-menopausal female) is willing to use effective contraceptive method for at least 30 days before Day 0 and at least 1 month after the last study drug administration. Effective contraceptive methods are:
- Barrier methods such as condom, sponge or diaphragm combined with spermicide in foam, gel or cream;
- Hormonal contraception (oral, intramuscular, implant or transdermal) which include Depo-Provera, Evra and Nuvaring;
- Intrauterine device (IUD);
- Sterilization such as tubal ligation, hysterectomy or vasectomy;
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- Postmenopausal state for at least 1 year for female subject or female partner of male subject;
- Same-sex partner;
- Abstinence.
- 3. Capable of giving informed consent and the consent must be obtained prior to any study related procedures.
- 4. Fitzpatrick skin phototypes II or III.
- 5. Subject weighs 100kg or less.
Who cannot join
- 1. Conditions or medications causing immunosuppression, photosensitization or phototoxicity.
- 2. Past history of skin cancer or subject having precancerous skin lesions (eg. actinic keratosis).
- 3. Subject has atopic dermatitis (cohort 1)
- 4. Subject has received investigational drugs within the 28 days or 5 half-lives, whichever is longer, prior to Day 0 or plans to during the study period.
- 5. Subject has used any topical medication on arms or buttocks within 14 days of Day 0 or plans to during the study.
- 6. At the investigator's discretion subject has current or past history of alcohol or drug abuse that would interfere with the ability of the subject to comply with the study protocol.
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- 7. Hypersensitivity/allergy to denosumab.
- 8. Hypersensitivity/allergy to lidocaine.
- 9. Hypersensitivity/allergy to latex.
- 10. Subject is taking anticoagulant medication except for low dose acetylsalicylic acid.
- 11. Past history of hypocalcemia or predisposing factors (eg, history of hypoparathyroidism, thyroid surgery, parathyroid surgery, malabsorption syndromes, excision of small intestine, severe renal impairment or receiving dialysis).
- 12. Known vitamin D deficiency.
- 13. Creatinine clearance less than 30mL/min (Cohort 2 only).
- 14. Corrected calcium concentration inferior to the normal range (Cohort 2 only).
- 15. Past history of osteonecrosis of the jaw (ONJ) or risk factors for ONJ (poor oral hygiene, periodontal and/or pre-existing dental disease, diagnosis of cancer with bone lesions, invasive dental procedures such as dental extractions or implants within 6 months of the screening visit.)
- 16. Past history of keloids or hypertrophic scarring.
- 17. Prior treatment with diphenylcyclopropenone.
- 18. Treatment with denosumab in the past 12 months.
- 19. Significant limitations in the range of motion of arms or shoulders.
Trial locations and contacts
1 site in 1 country.
About this study
Ultraviolet (UV) light is part of normal sunlight and has many effects on human skin and health. One of the harmful effects of long-term UV light exposure is that it can cause skin cancer. The mechanism by which UV light causes skin cancer is not entirely understood. One of the ways UV light causes cancer is by modifying DNA molecules in the cells of the skin. Another mechanism involved in cancer formation by UV light is immunosuppression. By this mechanism, UV light inactivates cells of the immune system of the skin. The immune cells are responsible for the detection and destruction of foreign substances and organisms such as bacterias and viruses but they also recognize and destroy cancer cells. UV light is known to prevent cells of the immune system to destroy cancer cells.
In laboratory experiments, a medication called denosumab has been shown to diminish the inhibition of ultraviolet-induced suppression of skin immunity. In other words, this medication could block the effect of UV on cells of the immune system and might allow patients taking this drug to be better protected from skin cancer.
Read more
The objective of this study is to test whether denosumab blocks the immunosuppressive effect of UVB light in healthy subjects. This study is divided into two stages. In the first stage, ten subjects (Cohort 1) will be sensitized to diphenylcyclopropenone (DPCP), a topical sensitizer commonly used for the treatment of alopecia areata and cutaneous warts. By reexposing the subjects to DPCP in incremental doses, dose-response levels of cutaneous hypersensitivity reactions in normal skin will be obtained. This will allow comparison of the normal levels of DPCP-induced cutaneous hypersensitivity (CHS) reaction in non UV-exposed skin (Cohort 1) to the CHS obtained from the two UVB-exposed experimental groups of Cohort 2.
In the second stage of the study, 20 subjects (Cohort 2) will be exposed to an immunosuppressive dose of ultraviolet B (UVB) 24 hours prior to DPCP sensitization. This is expected to result in the abolition of CHS upon rechallenge with DPCP. In order to assess whether denosumab can reverse UVB-induced immunosuppression, the subjects will have previously been randomized to receive a single 1mL injection of either 60 mg denosumab (group A; 10 subjects) or 1 mL saline (group B; 10 subjects) two weeks before UVB exposure. CHS reactions elicited by DPCP rechallenge will be compared between the denosumab and saline groups.
- Conditions
- Ultraviolet Rays, Immunosuppression, Hypersensitivity, Delayed, Immune Tolerance/Drug Effects
- Being tested
- Denosumab, UVB exposure, Diphenylcyclopropenone, Normal Saline
- Keywords
- Humans, Adult, skin, metabolism, radiation effects, Ultraviolet Rays, RANKL, RANK Ligand, denosumab, diphenylcyclopropenone, diphencyprone, immunology, immunosuppression, Antibodies, Monoclonal, Dermatitis, Allergic Contact, Hypersensitivity, Delayed
- Medical subject headings
- Hypersensitivity, Delayed, Dermatitis, Allergic Contact
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called Prolia
UVB exposureRadiation
Also called Ultraviolet B rays, Ultraviolet B light
DiphenylcyclopropenoneDrug
Also called Diphencyprone, DPCP
Normal SalineDrug
Also called Saline 0.9%, NaCl solution 0.9%
| Study group | Role | What they receive |
|---|---|---|
| DPCP alone (Cohort 1) | Other | Diphenylcyclopropenone sensitization patches applied for 48hours. Diphenylcyclopropenone elicitation patches applied for 48hours. Receives: Drug: Diphenylcyclopropenone |
| UVB and denosumab group (Cohort 2) | Experimental | Denosumab 60mg subcutaneous injection once. Broadband UVB exposure once. Diphenylcyclopropenone sensitization patches applied for 48hours. Diphenylcyclopropenone elicitation patches applied for 48hours. Receives: Drug: Denosumab; Radiation: UVB exposure; Drug: Diphenylcyclopropenone |
| UVB and placebo group (Cohort 2) | Placebo comparator | Normal saline 1mL subcutaneous injection once. Broadband UVB exposure once. Diphenylcyclopropenone sensitization patches applied for 48hours. Diphenylcyclopropenone elicitation patches applied for 48hours. Receives: Radiation: UVB exposure; Drug: Diphenylcyclopropenone; Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in dermal thickness: denosumab group vs placebo group of Cohort 2
Mean dermal thickness, as measured by 20 MHz ultrasonography, after challenge with incremental doses of DPCP for subjects randomized to denosumab as compared to subjects randomized to placebo.
Measured: Three weeks after sensitization to DPCP.
Secondary outcomes (7)
Clinical score of contact hypersensitivity reactions: denosumab group vs placebo group of Cohort 2
Mean clinical scores of contact hypersensitivity reaction sites elicited by incremental doses of DPCP challenges between the denosumab group and the placebo group.
Measured: Three weeks after sensitization to DPCP.
Diameters of contact hypersensitivity reactions: denosumab group vs placebo group of Cohort 2
Mean diameters (mm) of contact hypersensitivity reaction sites elicited by incremental doses of DPCP challenges between the denosumab group and the placebo group.
Measured: Three weeks after sensitization to DPCP.
Change in dermal thickness: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2)
Mean dermal thickness, as measured by 20 MHz ultrasonography, after challenge with incremental doses of DPCP for subjects previously exposed to UVB as compared to subjects non-exposed to UVB.
Measured: Three weeks after sensitization to DPCP.
Clinical score of contact hypersensitivity reactions: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2)
Mean clinical scores of contact hypersensitivity reaction sites elicited by incremental doses of DPCP between UV-exposed skin and non-UV exposed skin.
Measured: Three weeks after sensitization to DPCP.
Diameters of contact hypersensitivity reactions: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2)
Mean diameters of contact hypersensitivity reaction sites elicited by incremental doses of DPCP between UV-exposed skin and non-UV exposed skin.
Measured: Three weeks after sensitization to DPCP.
Gene expression levels: denosumab group vs placebo group of Cohort 2
Differences in gene expression levels of RANK, RANKL and proteins that are regulated by the RANK-RANKL interaction in the denosumab versus placebo groups.
Measured: At baseline, two weeks after treatment injection, and 24 hours after UVB exposure.
Histological pattern of expression of RANKL and other proteins of interest: denosumab group vs placebo group of Cohort 2
Differences in the cutaneous histological pattern of expression of RANK, RANKL and proteins and cells that are involved in RANK-RANKL interaction in the denosumab versus placebo groups.
Measured: At baseline, two weeks after treatment injection, and 24 hours after UVB exposure.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2013 (estimated)
- Study startNov 2013
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ultraviolet RaysStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Innovaderm Research Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert Bissonnette, MD, Principal investigator, Innovaderm Research Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01978483
- Sponsor's protocol ID
- Inno-6030
- Status last verified
- Jul 2014
- First submitted
- 31 Oct 2013
- Last updated
- 24 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of RANKL Inhibition on UV-induced Immunosuppression
- ClinicalTrials.gov ID
- NCT01978483
- Acronym / sponsor ID
- Inno-6030
- Conditions
- Ultraviolet Rays, Immunosuppression, Hypersensitivity, Delayed, Immune Tolerance/Drug Effects
- Keywords
- Humans, Adult, skin, metabolism, radiation effects, Ultraviolet Rays, RANKL, RANK Ligand
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Innovaderm Research Inc.University, hospital or other
- Study start
- Nov 2013
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 7 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ultraviolet (UV) light is part of normal sunlight and has many effects on human skin and health. One of the harmful effects of long-term UV light exposure is that it can cause skin cancer. The mechanism by which UV light causes skin cancer is not entirely understood. One of the ways UV light causes cancer is by modifying DNA molecules in the cells of the skin. Another mechanism involved in cancer formation by UV light is immunosuppression. By this mechanism, UV light inactivates cells of the immune system of the skin. The immune cells are responsible for the detection and destruction of foreign substances and organisms such as bacterias and viruses but they also recognize and destroy cancer cells. UV light is known to prevent cells of the immune system to destroy cancer cells.
In laboratory experiments, a medication called denosumab has been shown to diminish the inhibition of ultraviolet-induced suppression of skin immunity. In other words, this medication could block the effect of UV on cells of the immune system and might allow patients taking this drug to be better protected from skin cancer.
The objective of this study is to test whether denosumab blocks the immunosuppressive effect of UVB light in healthy subjects. This study is divided into two stages. In the first stage, ten subjects (Cohort 1) will be sensitized to diphenylcyclopropenone (DPCP), a topical sensitizer commonly used for the treatment of alopecia areata and cutaneous warts. By reexposing the subjects to DPCP in incremental doses, dose-response levels of cutaneous hypersensitivity reactions in normal skin will be obtained. This will allow comparison of the normal levels of DPCP-induced cutaneous hypersensitivity (CHS) reaction in non UV-exposed skin (Cohort 1) to the CHS obtained from the two UVB-exposed experimental groups of Cohort 2.
In the second stage of the study, 20 subjects (Cohort 2) will be exposed to an immunosuppressive dose of ultraviolet B (UVB) 24 hours prior to DPCP sensitization. This is expected to result in the abolition of CHS upon rechallenge with DPCP. In order to assess whether denosumab can reverse UVB-induced immunosuppression, the subjects will have previously been randomized to receive a single 1mL injection of either 60 mg denosumab (group A; 10 subjects) or 1 mL saline (group B; 10 subjects) two weeks before UVB exposure. CHS reactions elicited by DPCP rechallenge will be compared between the denosumab and saline groups.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| DPCP alone (Cohort 1) | Other | Drug: DiphenylcyclopropenoneDiphenylcyclopropenone sensitization patches applied for 48hours. Diphenylcyclopropenone elicitation patches applied for 48hours. |
| UVB and denosumab group (Cohort 2) | Experimental | Drug: Denosumab, Radiation: UVB exposure, Drug: DiphenylcyclopropenoneDenosumab 60mg subcutaneous injection once. Broadband UVB exposure once. Diphenylcyclopropenone sensitization patches applied for 48hours. Diphenylcyclopropenone elicitation patches applied for 48hours. |
| UVB and placebo group (Cohort 2) | Placebo comparator | Radiation: UVB exposure, Drug: Diphenylcyclopropenone, Drug: Normal SalineNormal saline 1mL subcutaneous injection once. Broadband UVB exposure once. Diphenylcyclopropenone sensitization patches applied for 48hours. Diphenylcyclopropenone elicitation patches applied for 48hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 1. Men or postmenopausal women 18 years of age or older at time of consent.
- 2. Male subject or his female partner (this criterion does not apply to post-menopausal female) is willing to use effective contraceptive method for at least 30 days before Day 0 and at least 1 month after the last study drug administration. Effective contraceptive methods are:
- 3. Capable of giving informed consent and the consent must be obtained prior to any study related procedures.
- 4. Fitzpatrick skin phototypes II or III.
- 5. Subject weighs 100kg or less.
Key exclusion criteria (19 listed)
- 1. Conditions or medications causing immunosuppression, photosensitization or phototoxicity.
- 2. Past history of skin cancer or subject having precancerous skin lesions (eg. actinic keratosis).
- 3. Subject has atopic dermatitis (cohort 1)
- 4. Subject has received investigational drugs within the 28 days or 5 half-lives, whichever is longer, prior to Day 0 or plans to during the study period.
- 5. Subject has used any topical medication on arms or buttocks within 14 days of Day 0 or plans to during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: Prolia | Drug | UVB and denosumab group (Cohort 2) |
| UVB exposureAlso: Ultraviolet B rays, Ultraviolet B light | Radiation | UVB and denosumab group (Cohort 2), UVB and placebo group (Cohort 2) |
| DiphenylcyclopropenoneAlso: Diphencyprone, DPCP | Drug | DPCP alone (Cohort 1), UVB and denosumab group (Cohort 2), UVB and placebo group (Cohort 2) |
| Normal SalineAlso: Saline 0.9%, NaCl solution 0.9% | Drug | UVB and placebo group (Cohort 2) |
Primary outcome
Change in dermal thickness: denosumab group vs placebo group of Cohort 2
Time frame: Three weeks after sensitization to DPCP.
Mean dermal thickness, as measured by 20 MHz ultrasonography, after challenge with incremental doses of DPCP for subjects randomized to denosumab as compared to subjects randomized to placebo.
7 secondary outcomes
Clinical score of contact hypersensitivity reactions: denosumab group vs placebo group of Cohort 2
Time frame: Three weeks after sensitization to DPCP.
Diameters of contact hypersensitivity reactions: denosumab group vs placebo group of Cohort 2
Time frame: Three weeks after sensitization to DPCP.
Change in dermal thickness: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2)
Time frame: Three weeks after sensitization to DPCP.
Clinical score of contact hypersensitivity reactions: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2)
Time frame: Three weeks after sensitization to DPCP.
Diameters of contact hypersensitivity reactions: non UV-exposed (Cohort 1) vs UV-exposed (Cohort 2)
Time frame: Three weeks after sensitization to DPCP.
Gene expression levels: denosumab group vs placebo group of Cohort 2
Time frame: At baseline, two weeks after treatment injection, and 24 hours after UVB exposure.
Histological pattern of expression of RANKL and other proteins of interest: denosumab group vs placebo group of Cohort 2
Time frame: At baseline, two weeks after treatment injection, and 24 hours after UVB exposure.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Bissonnette, MD principal investigator
Innovaderm Research Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Denosumab, UVB exposure and Diphenylcyclopropenone in people with Ultraviolet Rays and Immunosuppression, run by Innovaderm Research Inc. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in dermal thickness: denosumab group vs placebo group of Cohort 2 (time frame: Three weeks after sensitization to DPCP.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2014.