Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis

Phase 1

Terminated

Conditions: Psoriasis

Interventions: Drug: Humira Then Humira plus 3 B vitamins

Registration Number: NCT01704599

Lead Sponsor: Wayne State University

Brief Summary: Vitamins modulating homocysteine affect both TNF-alpha, vascular endothelial growth factor, and theoretically enhance the anti-inflammatory version of NOS thus hopefully increasing the efficacy and reducing the chance of some toxicities of adalimumab as determined by blood testing and EKGs.

Detailed Description: This is a pilot study designed to evaluate whether addition of oral vitamin B12, vitamin B6, and folic acid to the use of adalimumab for psoriasis leads to further improvement of a patient's psoriasis and quality of life.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 8

Inclusion Criteria

adults 18 or older
moderate to severe plaque psoriasis (>10% BSA)
Negative pregnancy test within 7 days before first dose of adalimumab in all women (except surgically sterile or 5 years postmenopausal)
subject must sign/date appropriate written informed consent&HIPAA authorization
Sexually active subjects of childbearing potential must agree to use medically acceptable contraception during screening and throughout the study
no evidence of active or latent tuberculosis based on a negative PPD skin test performed at screening, or within one year of starting this study. Patients with documentation of adequately treated TB may be enrolled
Patients PPD positive and CXR negative can be enrolled if they finish appropriate INH prophylaxis prior to enrollment
be willing and able to self-administer subcutaneous injections or to have a qualified person available to administer these injections
agrees to comply with protocol requirements, attend all regularly study visits and is considered to be a good study subject
meets concomitant medication washout requirements
willing to use only allowed psoriasis medications and treatments and agree not to start any topical, systemic, or phototherapy for psoriasis during the study period
adalimumab naïve

Exclusion Criteria

erythrodermic, pustular, or guttate psoriasis
skin conditions other than psoriasis that would interfere with study-related psoriasis evaluations
known sensitivity to any component of the study medications
Evidence of active infections such as fevers, chills, sweats, or history of untreated Lyme disease and active severe infections within 4 weeks before screening visit, or between the screening and Week 0 visits
history of listeriosis, untreated TB, persistent or active infections requiring hospitalization or treatment with IV antibiotics, IV antiretrovirals, or IV antifungals within 30 days of baseline, OR oral antibiotics, antivirals, or antifungals for purpose of treating infection, within 14 days of baseline
positive PPD and positive chest x-ray for latent or active tuberculosis
positive PPD and negative chest x-ray that have not completed appropriate INH prophylaxis
On immune compromising drug or history of immune compromising disorder or immunodeficiency
poorly controlled medical condition including, not limited to, unstable cardiovascular disease, poorly controlled diabetes, recent stroke, history of recurrent infections, or any condition for which, in the opinion of the investigators, participation in the study would place the subject at risk
hx. congestive heart failure
hx. demyelinating CNS disease
History of malignancy (other than previously treated localized carcinoma in situ of the cervix or previously treated nonmelanoma skin cancer)
history of or ongoing drug or alcohol abuse
past or present psychiatric morbidity which may compromise the study
Pregnant women, nursing mothers, or planning to become pregnant during study or within 150 days after last dose of study medication. Males planning pregnancy with spouse/partner while in study are to be excluded
plans to receive any live vaccines during study
history of liver disease
Current enrollment in another clinical study/treatment with other experimental drug or approved therapy for experimental use within 30 days prior to Week 0
previous enrollment in this study
cannot commit to all assessments required by the protocol
disorder that compromises the subject to give written informed consent and/or comply with study procedures
considered by the investigators to be unsuitable candidate
cannot comply with the protocol washout requirements
on folic acid in doses over than the minimal daily requirements
on vitamins higher than minimal daily requirements (multivitamins are allowed)
colon polyps or cancer
prior adalimumab therapy
on screening plasma Vascular Endothelial Growth Factor level is 140 pg/ml or more

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Humira then Humira plus 3 B vitamins	Humira Then Humira plus 3 B vitamins	Humira then Humira plus 3 B vitamins The only arm: After 16 weeks on adalimumab, modulators of homocysteine (oral vitamin B12, oral vitamin B6 or pyridoxine, and oral folic acid) will be added to adalimumab therapy for an additional 12 weeks. At end of this therapy can stop or continue. Telephone call day 70 after formal end of in person study the investigators will assess general health of each subject.

Primary Outcome Measures

Name	Time	Method
Number of Particpants With a Categorical PASI (Psoriasis Area and Severity Index) Change	Weeks 16 and 28	PASI: formula based on body surface areas on head/neck, trunk, both arms \& legs with disease quality grading induration, scale and erythema on participants ages 18-65 with moderate to severe plaque psoriasis measured at weeks 16 and 28.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With a Categorical Change in Static Physician Global Assessment (sPGA):	Week 16 and Week 28	Number of participants with a category change in Physician static Global Assessment (sPGA): 7 point score from 0 (clear) to 6 measuring amount of surface covered and plaque qualities: thickness \& erythema plus scaling. Dynamic score compares baseline with either improvement/ worsening of the same factors measured in the sPGA using the 0-6 scoring range but focused on change. sPGA at weeks 16 AND 28. dynamic PGA to be categoically measured at.weeks16 and 28.
Number of Participants With a Categorical DLQI (Dermatology Life Quality Index) Change	Week 16 and Week 28	DLQI is 10 questions examining impact of skin disease on quality of life: (1) symptoms \& feelings (2) daily activities (3) leisure (4) work \& school (5) personal relationship (6) treatment. To be administered to adults over 18 years with moderate to severe plaque psoriasis at week 0 (no systemic psoriasis medication);. weeks 16 ( after 16 weeks of adalimumab) and week 28 (after 16 weeks adalimumab then 12 weeks of adalimumab plus daily 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg B12).
Number of Participants With Category Change in Serum VEGF (Vascular Endothelial Growth Factorl)	At Screening visit, Week 16 on Humira, after another 12 weeks on Humira plus vitamins and if early termination	Adult particpants ages 18 or older with moderate to severe plaque psoriasis were to have serum VEGF measured at week 0 on no systemic psoriasis medication then at both weeks 16 on adalimumab and at week 28 on adalimumab plus folic acid, B6 and Vitamin B12. Subjects raniked by BMI week 0 low to high
Number of Participants With Category Change in Vitamin B12 Blood Level	At Week 16 and Week 28	Adult participants 18 years or older with moderate to severe plaque psoriasis were to have serum B12 levels measures Weeks 0 (on no systemic psoriasis medication), 16 (on adalimumab) and week 28 (on adalimumab plus daily 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg B12.
Number of Participants Within the Categories of Increasing and Decreasing Serum Homocysteine	Week 16 and Week 28	Serum homocysteine measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumaband then 12 weeks of adalimumab plus 5 mg folic acid, 100mg B6 and 1000 mcg of B12 in adults ages 18-65 with moderate to sever plaque psoriasis..
Number of Participants Within the Categories of Increasing and Decreasing Serum Vitamin B6 Level	At Week 16 and Week 28	Serum vitamin B6 levels were to be measured weeks16 after 16 weeks adalimumab and at week 28 after 16 weeks adalimumab and 12 weeks on adalimuamb, folic acid 5 mg, b6 100 mg and B12 1000 mcg in adult participants with moderate to sever plque psoriasis.
Number of Participants With Category Change in Serum Folic Acid Level.	Weeks 16 and 28	Serum folic acid level in adults ages 18 and older with mild to moderate plaque psoriasis measured at week 16 after 16 weeks adalimumab and at week 28 after 16 weeks adalimumab plus 12 weeks of adalimumab and daily 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg B12.