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Status unknownNCT03260166Updated Feb 2, 2021

Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus

A Phase 2 interventional study of nicotinamide in Cutaneous Lupus Erythematosus and Systemic Lupus Erythematosus Rash, sponsored by Second Xiangya Hospital of Central South University. Status unknown at 1 site in China. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2021-02-02.

Sponsored by Second Xiangya Hospital of Central South University · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jan 2021), so the status shown — last known as Active, not recruiting — may be out of date.
Phase
Phase 2
Study type
Interventional
Enrollment
40
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
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Study 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).

Read the 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.

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Conditions studied

  • Cutaneous Lupus Erythematosus
  • Systemic Lupus Erythematosus Rash

Keywords

  • nicotinamide
  • lupus-associated skin lesion
  • lupus erythematosus
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Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
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Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
40 participants (estimated)

Study arms

  • 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.

    Drug: nicotinamide

Interventions

  • Drugnicotinamide

    Drug: nicotinamide; Pharmaceutical form: tablet; Route of administration: oral

    Also known as: Niacinamide

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What researchers measure

Primary outcomes

  1. A change in Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) activity score

    The higher the RCLASI score, the worse of the lupus-associated skin lesion is.

    Time frame: from baseline (at visit 0) to 3 months treatment (at visit 3)

Secondary outcomes

  1. A change in RCLASI activity score

    The higher the RCLASI score, the worse of the lupus-associated skin lesion is.

    Time frame: from baseline (at visit 0) to 1, 2, 4, and 6 months treatment (at visit 1, 2, 4, and 5), respectively

  2. Response Rate and Remarkable Response Rate at 1, 2, 3, 4, and 6 months, respectively

    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.

    Time frame: 1 month, 2 months, 3 months, 4 months, and 6 months

  3. Number of Relapses

    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.

    Time frame: 4 months, 6 months

  4. A change in Dermatology Life Quality Index (DLQI) score

    DLQI reflect the quality of life related to skin manifestations.

    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

  5. 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

  6. A change in the percentage of different T helper cell (Th) subsets among CD4+ T lymphocytes

    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.

    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

  7. 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

    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.

    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

  8. A change in serum levels of complement 3 (C3), C4, and C1q

    This is for evaluation of the potential effects of nicotinamide on serum levels of complements that are associated with lupus activity

    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

  9. A change in the results of urine sediment test

    This is for evaluation of the potential effects of nicotinamide on renal damage.

    Time frame: 1 month, 2 months, 3 months, 4 months, and 6 months

  10. 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

  11. A change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index)

    This outcome is only evaluated for patients with SLE.

    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

  12. A change in British Isles Lupus Assessment Group 2004 Index (BILAG-2004)

    This outcome is only evaluated for patients with SLE.

    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

  13. Incidence of side effects

    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.

    Time frame: 3 months

  14. Incidence of side effects

    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.

    Time frame: 6 months

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Study locations

1 site
  • The Second Xiangya Hospital of Central South University
    Changsha, Hunan 410011, China
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References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03260166
Lead sponsor
Second Xiangya Hospital of Central South University
Collaborators
National Natural Science Foundation of China, Hunan Provincial Natural Science Foundation of China, National Key Clinical Specialty Construction Project of China
Responsible party
Qianjin Lu, MD, PhD (Professor and Director, Dept. of Dermatology, The Second Xiangya Hospital of Central South University, Central South University) — Principal investigator
First posted
Aug 24, 2017
Start date
Aug 31, 2017
Primary completion
Jan 1, 2020
Completion
Jul 1, 2021 (estimated)
Last update
Feb 2, 2021

Study contacts

Qianjin Lu, MD, PhD
principal investigator · Central South University

Oversight

FDA-regulated drug
No
FDA-regulated device
No
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