The Effect of Riboflavin on Moderate to Severe Plaque Type Psoriasis

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT02622386
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 2
• Actual Duration (Months): 43.8
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the anti-inflammatory effect of high-dose riboflavin supplementation on chronic plaque psoriasis. Psoriasis is a common chronic skin disorder that affects over 4 million people. There is no cure for psoriasis and treatment is directed at controlling patients' symptoms. Amongst patients with skin disease, there is significant interest in using complementary alternative medicine and vitamins to treat their disease. Previous human case reports suggest that riboflavin, commonly known as Vitamin B2, is clinically effective for the treatment of psoriasis; however, they were not conclusive. More recent human trials have shown that 400 mg of daily oral riboflavin is a safe and well-tolerated medication to administer to humans. For the purpose of this study, the riboflavin is used as an investigational drug.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Riboflavin; Other: Placebo	Phase 2

Detailed Description

The purpose of this investigation is to determine the anti-inflammatory effect of high-dose riboflavin supplementation on chronic plaque psoriasis. Up to fifty volunteers with chronic plaque psoriasis will be recruited for a double-blind, placebo-controlled 28 week prospective study with cross-over of both the intervention and control groups at the 12 week time mark. There will be a 4 week washout period when subjects crossover. Riboflavin will be dosed 400 mg by mouth daily versus placebo. Throughout the study the investigators will perform both clinical and laboratory assessments to measure response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: The Effect of Riboflavin on Moderate to Severe Plaque Type Psoriasis
• Actual Study Start Date: Aug 11, 2016
• Actual Primary Completion Date: Apr 6, 2020
• Actual Study Completion Date: Apr 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Riboflavin then Placebo Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks, followed by 4 week washout period before crossover. At crossover, patients will no longer receive Riboflavin but matching placebo capsule for additional 12 weeks.	Drug: Riboflavin; Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.; Other Names: Vitamin B2
Placebo Comparator: Placebo then Riboflavin Placebo oral capsule taken once daily for 12 weeks, followed by 4 week washout period before crossover. At crossover, patients will no longer receive placebo but 400 mg Riboflavin (Vitamin B2) capsule for additional 12 weeks.	Other: Placebo; Matching placebo capsule taken daily for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. Subjects Achieving 50% or Greater Psoriasis Area and Severity Index (PASI) Reduction [12 weeks]

   The number of subjects that achieve a 50 percent or greater reduction in their PASI with intervention as compared to placebo. The range of absolute PASI scores is 0-72, with higher scores indicating a greater severity of psoriasis. 0 to <5=Mild psoriasis; 5 to <10 = Moderate psoriasis; 10 to <72 = Severe psoriasis.

Secondary Outcome Measures

1. Subjects Achieving PASI 75, 90, 100 Response [12 weeks]

   The number of subjects that achieve a PASI 75, 90, 100 response with intervention as compared to placebo.

2. Subjects Achieving Physician Global Assessment (PGA) Score 0/1 [12 weeks]

   The number of subjects that achieve a PGA score of 0/1 with intervention as compared to placebo. The Global Assessment Scale is a simple instrument with a 9 point ordinal scoring system ranging from -4 indicating very marked worsening to +4 very marked improvement. This scale provides a subjective overall evaluation of treatment response by the patients/caregivers or physicians/health care providers.

3. Subjects Reporting Pruritus Score 0/1 [12 weeks]

   The number of subjects that report a pruritus score of 0/1 with intervention as compared to placebo. The pruritis scores can range from 0 to 10; where 0 means no itching and 10 means the worst itching.

4. Subjects Reporting Dermatology Life Quality Index (DLQI) Score 0/1 [12 weeks]

   The number of subjects treated that report a DLQI score of 0/1 with intervention as compared to placebo. Minimum score 0, maximum score of 30, where 0 means dermatological problems are not causing impairment on their quality of life and 30 means extreme negative impact of dermatological conditions. 0-1 = no effect at all on patient's life; 2-5 = small effect on patient's life; 6-10 = moderate effect on patient's life; 11-20 = very large effect on patient's life; 21-30 = extremely large effect on patient's life.

5. Difference in Riboflavin Serum Plasma Levels and Flavin-adenine Dinucleotide (FAD) [12 weeks]

   The difference in serum plasma levels of riboflavin and FAD in subjects treated with intervention as compared to placebo.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• 18 years of age or older

• Good general health

• Willingness and ability to follow the protocol

• Signed Informed Consent Form, written and witnessed.

• Stable moderate to severe chronic plaque psoriasis involving 8% or greater total body surface area (TBSA).

• If subject is a woman of childbearing potential, she must have a negative pregnancy test at screening and agree to use a medically acceptable form of contraception during the screening and throughout the study.

Exclusion Criteria:

• Started using a topical steroid stronger than moderate strength, vitamin A or D analog preparations, or anthralin within 14 days of study drug initiation.

• Initiated a systemic medications, including biologic medication, or phototherapy within 180 days of study drug initiation.

• Prior or concurrent use of cyclophosphamide.

• Currently using sulfasalazine therapy.

• Known hypersensitivity to riboflavin.

• Enrolled in any other investigational device or investigational drug trial(s) or receipt of any other investigational agent(s) within 28 days of baseline visit.

• Presence of severe comorbidities such as, diabetes mellitus requiring insulin; congestive heart failure (CHF) of any severity or myocardial infarction or cerebrovascular accident or transient ischemic attack within 3 months of screening visit; unstable angina pectoris, uncontrolled hypertension [sitting systolic BP <80 mm Hg or > 160 or diastolic BP > 100 mm Hg], oxygen-dependent severe pulmonary disease, history of cancer within 5 years [other than resected cutaneous basal or squamous cell carcinoma of the skin or in situ cervical cancer].

• Any of the following hematologic abnormalities, confirmed by repeat test at least 1 week apart:

1. White blood count <3,000/µL or >14,000/µL

2. Lymphocyte count <1,000/µL

3. Neutrophil count <1,5000/µL

4. Platelet count <150,000/µL

5. Hemoglobin<10 g/dL

• Liver function test aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AlkP) results that are greater than or equal to 2 times the upper limit of normal (ULN).

• Serum creatinine ≥ to 2x the ULN.

• Known HIV-positive status or known history of any other immune-suppressing disease.

• Any current or past history of psychiatric disease that would interfere with ability to comply with study protocol or give informed consent.

• Had grade 3 or 4 adverse events or infections within 28 days before screening, or between screening visit and drug initiation.

• Evidence of any skin conditions other than psoriasis that would interfere with the evaluations of the effect of study medication on psoriasis.

• Presence of any condition or circumstances judged by the patient's physician, the investigator, or medically qualified study staff to render this clinical trial detrimental or otherwise unsuitable for the patient's participation.

• A history of non-compliance with other therapies.

• Females who are pregnant, lactating, planning on pregnancy during the study period, or unwilling to use FDA-approved method of birth control.

• A history of keloids or excessive scar formation or of healing poorly.

• A history of allergic reaction to local anesthetics, including lidocaine and epinephrine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Department of Dermatology	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan

Investigators

• Principal Investigator: Johann Gudjonsson, MD, University of Michigan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 6, 2019

More Information

Publications

None provided.

• Responsible Party: Johann E Gudjonsson MD PhD, Assistant Professor of Dermatology, University of Michigan
• ClinicalTrials.gov Identifier: NCT02622386
• Other Study ID Numbers: HUM00105691 /Derm 677
• First Posted: Dec 4, 2015
• Last Update Posted: Jul 28, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Johann E Gudjonsson MD PhD, Assistant Professor of Dermatology, University of Michigan: Psoriasis
• Additional relevant MeSH terms: Psoriasis; Riboflavin

Study Results

Participant Flow

Arm/Group Title	Riboflavin Then Placebo	Placebo Then Riboflavin
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks, followed by 4 week washout period before crossover. At crossover, patients no longer received Riboflavin but matching placebo capsule for additional 12 weeks. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.	Placebo oral capsule taken once daily for 12 weeks, followed by 4 week washout period before crossover. At crossover, patients no longer received placebo but 400 mg Riboflavin (Vitamin B2) capsule for additional 12 weeks. Placebo: Matching placebo capsule taken daily for 12 weeks.
Period Title: First Assignment
STARTED	12	11
COMPLETED	9	9
NOT COMPLETED	3	2
Period Title: First Assignment
STARTED	9	9
COMPLETED	5	5
NOT COMPLETED	4	4
Period Title: First Assignment
STARTED	5	5
COMPLETED	5	3
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Because this is a crossover study, all Participants' data is combined.
Overall Participants	23
Age, Customized (Count of Participants)
22 - 29 Years of Age	1 4.3%
30 - 39 Years of Age	0 0%
40 - 49 Years of Age	8 34.8%
50 - 59 Years of Age	8 34.8%
60 - 69 Years of Age	5 21.7%
70 - 79 Years of Age	1 4.3%
Sex: Female, Male (Count of Participants)
Female	11 47.8%
Male	12 52.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	23 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 4.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 8.7%
White	20 87%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	23 100%
Psoriasis Area and Severity Index (PASI) at Baseline (score on a scale) [Mean (Full Range) ]
Mean (Full Range) [score on a scale]	8.7

Outcome Measures

1. Primary Outcome

Title	Subjects Achieving 50% or Greater Psoriasis Area and Severity Index (PASI) Reduction
Description	The number of subjects that achieve a 50 percent or greater reduction in their PASI with intervention as compared to placebo. The range of absolute PASI scores is 0-72, with higher scores indicating a greater severity of psoriasis. 0 to <5=Mild psoriasis; 5 to <10 = Moderate psoriasis; 10 to <72 = Severe psoriasis.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riboflavin	Placebo
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.	Placebo oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Placebo: Matching placebo capsule taken daily for 12 weeks.
Measure Participants	17	16
Count of Participants [Participants]	2 8.7%	2 NaN

2. Secondary Outcome

Title	Subjects Achieving PASI 75, 90, 100 Response
Description	The number of subjects that achieve a PASI 75, 90, 100 response with intervention as compared to placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riboflavin	Placebo
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.	Placebo oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Placebo: Matching placebo capsule taken daily for 12 weeks.
Measure Participants	17	16
PASI 75	0 0%	0 NaN
PASI 90	0 0%	0 NaN
PASI 100	0 0%	0 NaN

3. Secondary Outcome

Title	Subjects Achieving Physician Global Assessment (PGA) Score 0/1
Description	The number of subjects that achieve a PGA score of 0/1 with intervention as compared to placebo. The Global Assessment Scale is a simple instrument with a 9 point ordinal scoring system ranging from -4 indicating very marked worsening to +4 very marked improvement. This scale provides a subjective overall evaluation of treatment response by the patients/caregivers or physicians/health care providers.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riboflavin	Placebo
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.	Placebo oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Placebo: Matching placebo capsule taken daily for 12 weeks.
Measure Participants	17	16
Count of Participants [Participants]	2 8.7%	1 NaN

4. Secondary Outcome

Title	Subjects Reporting Pruritus Score 0/1
Description	The number of subjects that report a pruritus score of 0/1 with intervention as compared to placebo. The pruritis scores can range from 0 to 10; where 0 means no itching and 10 means the worst itching.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riboflavin	Placebo
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.	Placebo oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Placebo: Matching placebo capsule taken daily for 12 weeks.
Measure Participants	17	16
Count of Participants [Participants]	0 0%	2 NaN

5. Secondary Outcome

Title	Subjects Reporting Dermatology Life Quality Index (DLQI) Score 0/1
Description	The number of subjects treated that report a DLQI score of 0/1 with intervention as compared to placebo. Minimum score 0, maximum score of 30, where 0 means dermatological problems are not causing impairment on their quality of life and 30 means extreme negative impact of dermatological conditions. 0-1 = no effect at all on patient's life; 2-5 = small effect on patient's life; 6-10 = moderate effect on patient's life; 11-20 = very large effect on patient's life; 21-30 = extremely large effect on patient's life.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Riboflavin	Placebo
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.	Placebo oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Placebo: Matching placebo capsule taken daily for 12 weeks.
Measure Participants	17	16
Count of Participants [Participants]	2 8.7%	3 NaN

6. Secondary Outcome

Title	Difference in Riboflavin Serum Plasma Levels and Flavin-adenine Dinucleotide (FAD)
Description	The difference in serum plasma levels of riboflavin and FAD in subjects treated with intervention as compared to placebo.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Not available as assays were not able to be conducted.

Arm/Group Title	Riboflavin	Placebo
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.	Placebo oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Placebo: Matching placebo capsule taken daily for 12 weeks.
Measure Participants	0	0

Adverse Events

Time Frame	Participants were followed for 32 weeks (12 weeks of treatment 1; 4 weeks of washout; 12 weeks of treatment 2; and 4 weeks of followup)
Arm/Group Title	Riboflavin		Placebo
Arm/Group Description	Riboflavin (Vitamin B2) 400 mg oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Riboflavin: Riboflavin (Vitamin B2) 400 mg capsule taken daily for 12 weeks.		Placebo oral capsule taken once daily for 12 weeks either before or after a 4-week washout period. Placebo: Matching placebo capsule taken daily for 12 weeks.
All Cause Mortality
	Riboflavin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/16 (0%)
Serious Adverse Events
	Riboflavin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Riboflavin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/17 (52.9%)		7/16 (43.8%)
Cardiac disorders
elevated blood pressure	1/17 (5.9%)		0/16 (0%)
Eye disorders
eye itching	1/17 (5.9%)		0/16 (0%)
Gastrointestinal disorders
acid reflux flare	0/17 (0%)		1/16 (6.3%)
diarrhea	0/17 (0%)		1/16 (6.3%)
General disorders
fatigue	1/17 (5.9%)		1/16 (6.3%)
biopsy reaction	1/17 (5.9%)		1/16 (6.3%)
allergies	0/17 (0%)		2/16 (12.5%)
Hepatobiliary disorders
elevated liver enzymes	1/17 (5.9%)		0/16 (0%)
Infections and infestations
sinus infection	1/17 (5.9%)		1/16 (6.3%)
cold	1/17 (5.9%)		1/16 (6.3%)
24 hour Gastrointestinal event	0/17 (0%)		1/16 (6.3%)
upper respiratory infection	1/17 (5.9%)		0/16 (0%)
flu	1/17 (5.9%)		0/16 (0%)
Nervous system disorders
migraine aura	1/17 (5.9%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
nasal congestion	0/17 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
worsening psoriasis	1/17 (5.9%)		0/16 (0%)
folliculitis	0/17 (0%)		1/16 (6.3%)
Surgical and medical procedures
abdominal plasty	1/17 (5.9%)		0/16 (0%)

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.