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

NCT01704599 | Terminated Phase 1 Results DMC

• 1 other identifier: Dermatology 1104009591
• Study Type: interventional
• Target: 8
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Psoriasis

Keywords

Psoriasis; Adalimumab; B vitamins; Homocysteine; Folic acid; Cyanocobalamin; Pyridoxine; Vitamin B6; Vitamin B9; Vitamin B12

Outcome Measures

Primary Outcomes (1)

• Number of Particpants With a Categorical PASI (Psoriasis Area and Severity Index) Change

  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.

  Weeks 16 and 28

Secondary Outcomes (7)

• Number of Participants With a Categorical Change in Static Physician Global Assessment (sPGA):

  Week 16 and Week 28

• Number of Participants With a Categorical DLQI (Dermatology Life Quality Index) Change

  Week 16 and Week 28

• 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

• Number of Participants Within the Categories of Increasing and Decreasing Serum Homocysteine

  Week 16 and Week 28

• Number of Participants With Category Change in Vitamin B12 Blood Level

  At Week 16 and Week 28

Other Outcomes (12)

• Number of Participants in the Categories of Having and Not Having an Adverse Event

  After Week 16 of study

• Number of Participants in the Categories of Having and of Not Having a Serious Adverse Event (SAE)

  By Week 16, by Week 28 and by Day 70 post Week 28.

• Number of Participants in the Categories of Normalizing, Unchanging and Newly Abnormal Electrocardiograms (EKGs)

  Week 16 and then Week 28 after another 12 weeks on Humira plus vitamins and if early termination

Study Arms (1)

Humira then Humira plus 3 B vitamins

EXPERIMENTAL

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.

Drug: Humira Then Humira plus 3 B vitamins

Interventions

Humira Then Humira plus 3 B vitamins DRUG

Humira alone for 16 weeks then Humira plus 100 mg daily pyridoxine, 5 mg daily folic acid and 1000 mcg daily cyanocobalamin

Also known as: Humira, Adalimumab, Vitamin B6, Pyridoxine, Vitamin B9, Folic Acid, Vitamin B12, Cyanocobalamin

Humira then Humira plus 3 B vitamins

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wayne State University: lead
• Abbott: collaborator

Related Publications (11)

• 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.

  PMID: 20514802 BACKGROUND

• 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.

  PMID: 17087779 BACKGROUND

• 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.

  PMID: 10553943 BACKGROUND

• 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.

  PMID: 15083785 BACKGROUND

• 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.

  PMID: 17010738 BACKGROUND

• 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.

  PMID: 17444593 BACKGROUND

• 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.

  PMID: 17305904 BACKGROUND

• 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.

  PMID: 21173304 BACKGROUND

• 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.

  PMID: 20953189 BACKGROUND

• 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/

  PMID: 23193625 BACKGROUND

• 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.

  PMID: 20861854 BACKGROUND

Related Links

• Search for Humira
• hypermagnesemia

MeSH Terms

Conditions

Psoriasis

Interventions

Adalimumab; Vitamin B 6; Pyridoxine; Folic Acid; Vitamin B 12

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Picolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

Early termination due to high amount of combination of side effects and poor outcomes leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Peter J. Aronson, MD
• Organization: Dept. Dermatology Wayne StateUniversity

paronson@med.wayne.edu

(313)_745-7845

Study Officials

• Peter J Aronson, MD

  Department Dermatology Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor Department of Dermatology

Study Record Dates

• First Submitted: October 3, 2012
• First Posted: October 11, 2012
• Study Start: January 1, 2009
• Primary Completion: June 1, 2013
• Study Completion: May 1, 2014
• Last Updated: February 4, 2015
• Results First Posted: February 4, 2015

Record last verified: 2015-01