Clinical trial NCT03260166: Nicotinamide Treatment for Lupus-associated Skin Lesions in Lupus Erythematosus
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Cutaneous Lupus Erythematosus
Systemic Lupus Erythematosus Rash
Keywords: nicotinamide
lupus-associated skin lesion
lupus erythematosus
Lead sponsor: Second Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
name: Hunan Provincial Natural Science Foundation of China
name: National Key Clinical Specialty Construction Project of China
First posted: 2017-08-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: A change in Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI) activity score
timeFrame: from baseline (at visit 0) to 3 months treatment (at visit 3)
Secondary outcomes:
measure: A change in RCLASI activity score
timeFrame: from baseline (at visit 0) to 1, 2, 4, and 6 months treatment (at visit 1, 2, 4, and 5), respectively
measure: Response Rate and Remarkable Response Rate at 1, 2, 3, 4, and 6 months, respectively
timeFrame: 1 month, 2 months, 3 months, 4 months, and 6 months
measure: Number of Relapses
timeFrame: 4 months, 6 months
measure: A change in Dermatology Life Quality Index (DLQI) score
timeFrame: 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
measure: A change in Physician's Global Assessment (PGA) score
timeFrame: 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
measure: A change in the percentage of different T helper cell (Th) subsets among CD4+ T lymphocytes
timeFrame: 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
measure: 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
timeFrame: 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
measure: A change in serum levels of complement 3 (C3), C4, and C1q
timeFrame: 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
measure: A change in the results of urine sediment test
timeFrame: 1 month, 2 months, 3 months, 4 months, and 6 months
measure: Dose reduction of concomitant corticosteroids
timeFrame: from baseline (at visit 0) to 3 months, 4 months, and 6 months (at visit 3, 4, and 5), respectively
measure: A change in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the systemic lupus erythematosus disease activity index)
timeFrame: 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
measure: A change in British Isles Lupus Assessment Group 2004 Index (BILAG-2004)
timeFrame: 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
measure: Incidence of side effects
timeFrame: 3 months
measure: Incidence of side effects
timeFrame: 6 months
Other outcomes:
Locations:
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: Central South University
name: Qianjin Lu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: