Clinical trial NCT01704599: Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis
Official title: A Single-Center, Open-Label Study to Assess the Effects of the Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis Evaluated With the PASI, PGA and DLQI
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Psoriasis
Keywords: Psoriasis
Adalimumab
B vitamins
Homocysteine
Folic acid
Cyanocobalamin
Pyridoxine
Vitamin B6
Vitamin B9
Vitamin B12
Lead sponsor: Wayne State University
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2012-10-11
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Particpants With a Categorical PASI (Psoriasis Area and Severity Index) Change
timeFrame: Weeks 16 and 28
Secondary outcomes:
measure: Number of Participants With a Categorical Change in Static Physician Global Assessment (sPGA):
timeFrame: Week 16 and Week 28
measure: Number of Participants With a Categorical DLQI (Dermatology Life Quality Index) Change
timeFrame: Week 16 and Week 28
measure: Number of Participants With Category Change in Serum VEGF (Vascular Endothelial Growth Factorl)
timeFrame: At Screening visit, Week 16 on Humira, after another 12 weeks on Humira plus vitamins and if early termination
measure: Number of Participants Within the Categories of Increasing and Decreasing Serum Homocysteine
timeFrame: Week 16 and Week 28
measure: Number of Participants With Category Change in Vitamin B12 Blood Level
timeFrame: At Week 16 and Week 28
measure: Number of Participants Within the Categories of Increasing and Decreasing Serum Vitamin B6 Level
timeFrame: At Week 16 and Week 28
measure: Number of Participants With Category Change in Serum Folic Acid Level.
timeFrame: Weeks 16 and 28
Other outcomes:
measure: Number of Participants in the Categories of Having and Not Having an Adverse Event
timeFrame: After Week 16 of study
measure: Number of Participants in the Categories of Having and of Not Having a Serious Adverse Event (SAE)
timeFrame: By Week 16, by Week 28 and by Day 70 post Week 28.
measure: Number of Participants in the Categories of Normalizing, Unchanging and Newly Abnormal Electrocardiograms (EKGs)
timeFrame: Week 16 and then Week 28 after another 12 weeks on Humira plus vitamins and if early termination
measure: Number of Participants in Categories or Increasing and Decreasing Changes Within the CBC (Complete Blood Count)
timeFrame: Week 16 and Week 28
measure: Number of Participants Within the Categories of Increasing and Decreasing Serum Magnesium
timeFrame: Weeks 16 and 28
measure: Number of Participants Within the Categories of Increasing and Decreasing Serum Phosphorus
timeFrame: Week 16 then Week 28
measure: Number of Participants Within the Categories of Elevated and Normal Helicobacter Pylori Antibody
timeFrame: Week 28 after 16 weeks of Adalimumab then 12 of Adalimumab-Vitamins
measure: Number of Participants Within the Categories of Positive Urine Pregnancy Test (Urine Hcg)
timeFrame: At screening
measure: Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures:
timeFrame: Week 16 and Week 28
measure: Number of Participants Within Categories of Body Temperature Change
timeFrame: Weeks 16 and 28
measure: Number of Participants Who Fulfilled the Category of Having Height Measured
timeFrame: Week 0 at Start of Adalimumab
measure: Number of Participants Within the Categories of Increasign and Decreasing Body Weight
timeFrame: Week 16 and Week 28
Locations:
Study officials:
affiliation: Department Dermatology Wayne State University
name: Peter J Aronson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aronson PJ, Malick F. Towards rational treatment of severe psoriasis in alcoholics: report of two cases. J Drugs Dermatol. 2010 Apr;9(4):405-8.
citation: Moat SJ, Madhavan A, Taylor SY, Payne N, Allen RH, Stabler SP, Goodfellow J, McDowell IF, Lewis MJ, Lang D. High- but not low-dose folic acid improves endothelial function in coronary artery disease. Eur J Clin Invest. 2006 Dec;36(12):850-9. doi: 10.1111/j.1365-2362.2006.01739.x.
citation: Li W, Zheng T, Wang J, Altura BT, Altura BM. Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular free magnesium ions in canine cerebral vascular smooth muscle cells: possible relationship to [Ca2+]i, atherogenesis and stroke. Neurosci Lett. 1999 Oct 22;274(2):83-6. doi: 10.1016/s0304-3940(99)00683-7.
citation: Lewis V, Finlay AY. 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc. 2004 Mar;9(2):169-80. doi: 10.1111/j.1087-0024.2004.09113.x. No abstract available.
citation: Gordon KB, Langley RG, Leonardi C, Toth D, Menter MA, Kang S, Heffernan M, Miller B, Hamlin R, Lim L, Zhong J, Hoffman R, Okun MM. Clinical response to adalimumab treatment in patients with moderate to severe psoriasis: double-blind, randomized controlled trial and open-label extension study. J Am Acad Dermatol. 2006 Oct;55(4):598-606. doi: 10.1016/j.jaad.2006.05.027. Epub 2006 Aug 10.
citation: Genovese MC, Mease PJ, Thomson GT, Kivitz AJ, Perdok RJ, Weinberg MA, Medich J, Sasso EH; M02-570 Study Group. Safety and efficacy of adalimumab in treatment of patients with psoriatic arthritis who had failed disease modifying antirheumatic drug therapy. J Rheumatol. 2007 May;34(5):1040-50. Epub 2007 Apr 15.
citation: Pitarch G, Sanchez-Carazo JL, Mahiques L, Perez-Ferriols MA, Fortea JM. Treatment of psoriasis with adalimumab. Clin Exp Dermatol. 2007 Jan;32(1):18-22. doi: 10.1111/j.1365-2230.2006.02288.x.
citation: Leonardi C, Langley RG, Papp K, Tyring SK, Wasel N, Vender R, Unnebrink K, Gupta SR, Valdecantos WC, Bagel J. Adalimumab for treatment of moderate to severe chronic plaque psoriasis of the hands and feet: efficacy and safety results from REACH, a randomized, placebo-controlled, double-blind trial. Arch Dermatol. 2011 Apr;147(4):429-36. doi: 10.1001/archdermatol.2010.384. Epub 2010 Dec 20.
citation: Stuart PE, Nair RP, Ellinghaus E, Ding J, Tejasvi T, Gudjonsson JE, Li Y, Weidinger S, Eberlein B, Gieger C, Wichmann HE, Kunz M, Ike R, Krueger GG, Bowcock AM, Mrowietz U, Lim HW, Voorhees JJ, Abecasis GR, Weichenthal M, Franke A, Rahman P, Gladman DD, Elder JT. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet. 2010 Nov;42(11):1000-4. doi: 10.1038/ng.693. Epub 2010 Oct 17.
citation: Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998. Available from http://www.ncbi.nlm.nih.gov/books/NBK114310/
citation: Suarez-Farinas M, Fuentes-Duculan J, Lowes MA, Krueger JG. Resolved psoriasis lesions retain expression of a subset of disease-related genes. J Invest Dermatol. 2011 Feb;131(2):391-400. doi: 10.1038/jid.2010.280. Epub 2010 Sep 23.