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Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT03260166
Recruitment Status : Unknown
Verified September 2017 by Qianjin Lu, MD, PhD, Central South University.
Recruitment status was:  Recruiting
First Posted : August 24, 2017
Last Update Posted : September 25, 2017
Sponsor:
Collaborators:
National Natural Science Foundation of China
Hunan Provincial Natural Science Foundation of China
National Key Clinical Specialty Construction Project of China
Information provided by (Responsible Party):
Qianjin Lu, MD, PhD, Central South University

Tracking Information
First Submitted Date  ICMJE August 10, 2017
First Posted Date  ICMJE August 24, 2017
Last Update Posted Date September 25, 2017
Actual Study Start Date  ICMJE August 31, 2017
Estimated Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 21, 2017)
A change in Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) activity score [ Time Frame: from baseline (at visit 0) to 3 months treatment (at visit 3) ]
The higher the RCLASI score, the worse of the lupus-associated skin lesion is.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03260166 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 25, 2017)
  • A change in RCLASI activity score [ Time Frame: from baseline (at visit 0) to 1, 2, 4, and 6 months treatment (at visit 1, 2, 4, and 5), respectively ]
    The higher the RCLASI score, the worse of the lupus-associated skin lesion is.
  • Response Rate and Remarkable Response Rate at 1, 2, 3, 4, and 6 months, respectively [ Time Frame: 1 month, 2 months, 3 months, 4 months, and 6 months ]
    Response is defined as a ≥ 4-point reduction or a ≥20% reduction in RCALSI activity score. Remarkable Response is defined as a ≥50% reduction in RCALSI activity score.
  • Number of Relapses [ Time Frame: 4 months, 6 months ]
    Relapse means that if the patient's RCLASI activity score has a ≥ 4-point reduction or a ≥20% reduction than at baseline during the 3-month treatment, and then the RCLASI activity score increase to be no lower than at baseline after stopping using nicotinamide in the following 3 months.
  • A change in Dermatology Life Quality Index (DLQI) score [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    DLQI reflect the quality of life related to skin manifestations.
  • A change in Physician's Global Assessment (PGA) score [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
  • A change in the percentage of different T helper cell (Th) subsets among CD4+ T lymphocytes [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    At each time point, the percentage of Th1, Th2, Th17, regulatory T cell (Treg), and follicular helper T cell (Tfh) subsets among CD4+ T lymphocytes in peripheral venous blood of the patient will be measured by flow cytometry. 5 ml of peripheral venous blood will be collected from the patient at each time point, of which 4.5 ml will be used in this flow cytometry assay.
  • A change in the serum level of cytokines interferon (IFN)γ, interleukin (IL)-4, IL-17A, transforming growth factor (TGF)-β, IL-10, IL-21, and IL-6 [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    At each time point, the serum level of cytokines IFNγ, IL-4, IL-17A, TGF-β, IL-10, IL-21, and IL-6 in the patient's venous blood will be measured using enzyme linked immunosorbent assay (ELISA) or Bio-Plex methods. 5 ml of peripheral venous blood will be collected from the patient at each time point, of which 0.5 ml will be used in this ELISA or Bio-Plex assay.
  • A change in serum levels of complement 3 (C3), C4, and C1q [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    This is for evaluation of the potential effects of nicotinamide on serum levels of complements that are associated with lupus activity
  • A change in the results of urine sediment test [ Time Frame: 1 month, 2 months, 3 months, 4 months, and 6 months ]
    This is for evaluation of the potential effects of nicotinamide on renal damage.
  • Dose reduction of concomitant corticosteroids [ Time Frame: from baseline (at visit 0) to 3 months, 4 months, and 6 months (at visit 3, 4, and 5), respectively ]
  • A change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index) [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    This outcome is only evaluated for patients with SLE.
  • A change in British Isles Lupus Assessment Group 2004 Index (BILAG-2004) [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    This outcome is only evaluated for patients with SLE.
  • Incidence of side effects [ Time Frame: 3 months ]
    Possible side effects of nicotinamide include flushing and itching of the skin, cardiac arrhythmia, dizziness, nausea, epigastric discomfort, loss of appetite, elevated blood glucose, and elevated blood uric acid. The major side effects of HCQ that need to be monitored include retina toxicity.
  • Incidence of side effects [ Time Frame: 6 months ]
    Possible side effects of nicotinamide include flushing and itching of the skin, cardiac arrhythmia, dizziness, nausea, epigastric discomfort, loss of appetite, elevated blood glucose, and elevated blood uric acid. The major side effects of HCQ that need to be monitored include retina toxicity.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2017)
  • A change in RCLASI activity score [ Time Frame: from baseline (at visit 0) to 1, 2, 4, and 6 months treatment (at visit 1, 2, 4, and 5), respectively ]
    The higher the RCLASI score, the worse of the lupus-associated skin lesion is.
  • Response Rate and Remarkable Response Rate at 1, 2, 3, 4, and 6 months, respectively [ Time Frame: 1 month, 2 months, 3 months, 4 months, and 6 months ]
    Response is defined as a ≥ 4-point reduction or a ≥20% reduction in RCALSI activity score. Remarkable Response is defined as a ≥50% reduction in RCALSI activity score.
  • Number of Relapses [ Time Frame: 4 months, 6 months ]
    Relapse means that if the patient's RCLASI activity score has a ≥ 4-point reduction or a ≥20% reduction than at baseline during the 3-month treatment, and then the RCLASI activity score increase to be no lower than at baseline after stopping using nicotinamide in the following 3 months.
  • A change in Dermatology Life Quality Index (DLQI) score [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    DLQI reflect the quality of life related to skin manifestations.
  • A change in Physician's Global Assessment (PGA) score [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
  • A change in the percentage of different T helper cell (Th) subsets among CD4+ T lymphocytes [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    At each time point, the percentage of Th1, Th2, Th17, regulatory T cell (Treg), and follicular helper T cell (Tfh) subsets among CD4+ T lymphocytes in peripheral venous blood of the patient will be measured by flow cytometry. 5 ml of peripheral venous blood will be collected from the patient at each time point, of which 4.5 ml will be used in this flow cytometry assay.
  • A change in the serum level of cytokines interferon (IFN)γ, interleukin (IL)-4, IL-17A, transforming growth factor (TGF)-β, IL-10, IL-21, and IL-6 [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    At each time point, the serum level of cytokines IFNγ, IL-4, IL-17A, TGF-β, IL-10, IL-21, and IL-6 in the patient's venous blood will be measured using enzyme linked immunosorbent assay (ELISA) or Bio-Plex methods. 5 ml of peripheral venous blood will be collected from the patient at each time point, of which 0.5 ml will be used in this ELISA or Bio-Plex assay.
  • A change in serum levels of complement 3 (C3), C4, and C1q [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    This is for evaluation of the potential effects of nicotinamide on serum levels of complements that are associated with lupus activity
  • A change in the results of urine sediment test [ Time Frame: 1 month, 2 months, 3 months, 4 months, and 6 months ]
    This is for evaluation of the potential effects of nicotinamide on renal damage.
  • Dose reduction of concomitant corticosteroids [ Time Frame: from baseline (at visit 0) to 3 months, 4 months, and 6 months (at visit 3, 4, and 5), respectively ]
  • A change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index) [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    This outcome is only evaluated for patients with SLE.
  • A change in British Isles Lupus Assessment Group 2004 Index (BILAG-2004) [ Time Frame: from baseline (at visit 0) to 1 month, 2 months, 3 months, 4 months, and 6 months (at visit 1, 2, 3, 4, and 5), respectively ]
    This outcome is only evaluated for patients with SLE.
  • Incidence of side effects [ Time Frame: 1 month, 2 months, 3 months, 4 months, and 6 months ]
    Possible side effects of nicotinamide include flushing and itching of the skin, cardiac arrhythmia, dizziness, nausea, epigastric discomfort, loss of appetite, elevated blood glucose, and elevated blood uric acid. The major side effects of HCQ that need to be monitored include retina toxicity.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus
Official Title  ICMJE An Open-label Study for Assessing the Efficacy and Safety of Nicotinamide Treatment for Lupus-associated Skin Lesions in Patients With Cutaneous Lupus Erythematosus or Systemic Lupus Erythematosus
Brief Summary This clinical study will test the efficacy and safety of nicotinamide for lupus-associated skin lesions refractory to the treatment of hydroxychloroquine plus low-dose corticosteroids in patients with cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE).
Detailed Description

Backgrounds: Lupus erythematosus (LE) is an autoimmune disease affecting various organs. Lupus-associated skin lesions are the dominant clinical manifestations of cutaneous lupus erythematosus (CLE) and also occur in 70%~80% of patients with systemic lupus erythematosus (SLE), and usually involve the sunlight-exposure sites such as the face, neck and hands, which affects the personal appearance dramatically and causes substantial psychological impact to the patients.

While antimalarials such as hydroxychloroquine (HCQ) have been widely used as a first-line treatment for lupus-associated skin lesions, 30% of patients with lupus do not respond to this medication. Other available therapies such as corticosteroids and thalidomide can also be applied, however, their toxic side effects limit the clinical use. Recent studies by the investigators have shown that nicotinamide, a water-soluble vitamin whose side effects are considered as minimal, can protect MRL/lpr mice (a lupus-like mouse model) from skin lesions and autoantibody production. Thus it is hypothesized that nicotinamide treatment could be a novel therapy for lupus-associated skin lesions in patients with LE.

Design of Study: This is a single center, uncontrolled, open-label study to assess the efficacy and safety of nicotinamide for lupus-associated skin lesions refractory to the treatment of HCQ plus low-dose corticosteroids in patients with CLE or SLE.

Methods: For CLE or SLE patients with lupus-associated skin lesions scoring >=4 on the Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) that have been refractory to the treatment of HCQ plus low-dose corticosteroids (<=0.5 mg/kg/d) during the past two months, oral nicotinamide (500 mg twice daily) will be given consecutively for 3 months while the current regimen including HCQ and corticosteroids be maintained without change. The end points include clinical response and immunological changes, as well as safety.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Cutaneous Lupus Erythematosus
  • Systemic Lupus Erythematosus Rash
Intervention  ICMJE Drug: nicotinamide
Drug: nicotinamide; Pharmaceutical form: tablet; Route of administration: oral
Other Name: Niacinamide
Study Arms  ICMJE Experimental: nicotinamide
Patients will receive 10 nicotinamide tablets orally twice daily (nicotinamide 500 mg, p.o., Bid) for a period of 3 months. Each tablet contains 50 mg of nicotinamide.
Intervention: Drug: nicotinamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: August 21, 2017)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2019
Estimated Primary Completion Date August 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age: between 18 years and 65 years.
  2. Patients clinically and histopathologically diagnosed as cutaneous lupus erythematosus (CLE) that have not respond to treatment with hydroxychloroquine (200-400 mg/day) plus corticosteroids at a dosage less than the equivalent of 0.5mg/kg/day of prednisone for the preceding two months or a longer period.
  3. Patients diagnosed as SLE (meeting the 1997 American College of Rheumatology criteria for SLE) that present with lupus-associated skin lesions that have not respond to treatment with hydroxychloroquine (200-400 mg/day) plus corticosteroids at a dosage less than the equivalent of 0.5mg/kg/day of prednisone for the preceding two months or a longer period.
  4. Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) ≥4; for patients with SLE, Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index (SELENA-SLEDAI) is within the range between 0 and 9.
  5. Written informed consent form.

Exclusion Criteria:

  1. Severe comorbidities including heart failure (≥grade III NYHA), respiratory failure, renal insufficiency (creatinine clearance ≤30 ml/min), hepatic insuf¬ficiency (alanine aminotransferase or aspartate aminotransferase ≥2 times of the upper limit of the normal range), or active severe neuropsychiatric manifestations of SLE.
  2. Acute severe infection such as sepsis and cellulitis, or a history of infection of hepatitis B or C virus, Mycobacterium tuberculosis, or human immunodeficiency virus (HIV).
  3. A history of treatment with nicotinamide, niacin, or multi-vitamins in the recent month.
  4. A history of treatment with rituximab or other biologics; or a history of treatment with high-dose corticosteroids (≥1.5 mg/kg/d), immunosuppressants, tripterygium glycosides, or intravenous immunoglobin G (IVIG) in the preceding three months.
  5. Patients not suitable for using nicotinamide due to comorbidities including pruritic skin diseases such as atopic dermatitis and urticaria, vertigo, dizziness, headache, hyperglycemia, and hyperuricemia; patients not suitable for using hydroxychloroquine due to conditions including retinopathy or hypersensitivity to hydroxychloroquine.
  6. Patients with drug abuse, alcohol abuse, or mental disorders that are unable to cooperate or adhere to treatment.
  7. Pregnancy or lac¬tation in females.
  8. Participants in other clinical trials.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03260166
Other Study ID Numbers  ICMJE PFK201707
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Qianjin Lu, MD, PhD, Central South University
Study Sponsor  ICMJE Second Xiangya Hospital of Central South University
Collaborators  ICMJE
  • National Natural Science Foundation of China
  • Hunan Provincial Natural Science Foundation of China
  • National Key Clinical Specialty Construction Project of China
Investigators  ICMJE
Principal Investigator: Qianjin Lu, MD, PhD Central South University
PRS Account Second Xiangya Hospital of Central South University
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP