Clinical trial NCT06079788: Study of Adrenocorticotropic Hormone on Children With Frequent Relapse or Steroid-dependent Nephrotic Syndrome: a Prospective, Multicenter, Randomized，Open-label Clinical Trial.
Official title: Study of Adrenocorticotropic Hormone on Children With Frequent Relapse or Steroid-dependent Nephrotic Syndrome: a Prospective, Multicenter, Randomized，Open-label Clinical Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Nephrotic Syndrome in Children
Keywords: Nephrotic Syndrome
Frequently Relapsing Nephrotic Syndrome
Steroid Dependent Nephrotic Syndrome
Adrenocorticotropic Hormone
Lead sponsor: The Children's Hospital of Zhejiang University School of Medicine
Sponsor class: OTHER
Collaborators: name: Tongji Hospital
name: Children's Hospital affiliated to Capital Institute of Pediatrics
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Children's Hospital of Nanjing Medical University
name: Kunming Children's Hospital
name: Yuying Childrens Hospital of Wenzhou Medical University
name: Ningbo Women & Children's Hospital
First posted: 2023-10-12
Enrollment: 140
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary nephrotic syndrome accounts for approximately 90% of the total number of nephrotic syndrome in childhood and it is the most common glomerular disease in children. Although treatment with steroids is useful for primary nephrotic syndrome, proving to cause frequent relapse/steroid-dependent nephrotic syndrome after treatment and the usage of immunosuppressive agents has become a new choice for the treatment of such patients. This study is a prospective, multicenter, randomized，open-label clinical trial, evaluating the efficacy and safety of steroid combined with adrenocorticotrophic hormone（ACTH） to children who with frequently relapsing or steroid-dependent nephrotic syndrome, all we wish to obtain the proper drug choice and individualized treatment options for children with nephrotic syndrome.

Detailed description: Although steroids are recognized as first-line treatments for nephrotic syndrome, the vast majority of children relapse, and about half of them have frequent relapse or steroids dependence after treatment with steroids alone. Some children experienced steroids-resistance after multiple relapses, and eventually developed into chronic kidney dysfunction. Long-term or repeated application of large doses of steroids will lead to side effects such as obesity, growth retardation, and hypertension. Although the treatment of steroids with immunosuppressive agents is a new choice for the treatment of such patients, traditional immunosuppressive agents will bring some serious irreversible side effects.

The clinical application of ACTH in children with nephrotic syndrome dates back to the late 1940s. In recent years, the new mechanism of action of ACTH is also being explored. A number of clinical studies on the treatment of nephrotic syndrome by ACTH have found that it can still achieve good efficacy in patients who are ineffective in first-line treatment. This study evaluated the efficacy of ACTH in the treatment of relapsing or steroid-dependent nephrotic syndrome in children, in order to provide a more effective and safer treatment for children with nephrotic syndrome as well as the therapeutic medication options.

Eligibility criteria: Inclusion Criteria:

1. Age 2-14 years old;
2. Sensitive but frequent relapses or steroids dependence nephrotic syndrome
3. No severe hormonal side effects and/or low-dose steroids dependent idiopathic nephrotic syndrome in children (defined as two relapses with an average dose \< 0.5mg/kg/day or equivalent alternate-day dose)
4. Normal renal function: eGFR≥90ml/min/1.73m2;
5. Morning urine protein \<1+ or urine protein-creatinine ratio \<0.2g/g (\<20 mg/mmol) for 3 consecutive days and above when in enroll;
6. Prednisone dose was 1.5-2 mg/kg per day before admission;
7. No use of other immunosuppressants (such as tacrolimus, mortecophenolate, cyclosporin A, cyclophosphamide, levamisole, imidazole ribin, or tripterygium, etc.) within 3 months, and no use of rituximab or beliumab within 6 months.

Exclusion Criteria:

1. Family history of nephrotic syndrome, chronic glomerulonephritis, uremia and other kidney diseases;
2. Patients with congenital or acquired immunodeficiency, or with active tuberculosis, active CMV, EBV, hepatitis B, hepatitis C, HIV infection, deep fungal infection, or other active infections;
3. Recurrent or persistent hypertension;
4. Secondary nephrotic syndrome, such as nephrotic syndrome secondary to systemic lupus erythematosus, diabetes, drug poisoning and infection;
5. Combined with other kidney diseases, such as polycystic kidney, ANCA vasculitis, urinary system malformations, etc.;
6. Patients with hypertension, diabetes, tuberculosis, suppurative or fungal infection, gastric and duodenal ulcer disease and heart failure; Patients with other serious heart, liver and other important organs, blood system, endocrine system and other system lesions;
7. Co-occurrence of other monogenic genetic diseases known to affect the condition of nephrotic syndrome;
8. Patients with serious autoimmune diseases or tumors;
9. Use of other immunosuppressants (such as tacrolimus, mortecophenolate, cyclosporin A, cyclophosphamide, levamisole, imidazole ribin, or tripterygium, etc.) within 3 months, and no use of rituximab or beliumab within 6 months;
10. Patients who are known to be allergic to ACTH, glucocorticoids, or any of the components of these drugs, and patients with severe hormone-related side effects
11. History of organ transplantation (excluding corneal and hair transplantation);
12. Patients who had participated in other clinical trials within three months prior to enrollment;
13. Any patient whom the investigator determines is not suitable for inclusion in the trial.

Primary outcomes:
measure: Recurrence-free survival time(day) within 48 weeks
timeFrame: Within 48 weeks after randomization
Secondary outcomes:
measure: Number of relapses during 48 weeks follow up
timeFrame: Within 48 weeks after randomization
measure: The first time to relapse
timeFrame: Within 48 weeks after randomization
measure: Cumulative prednisone dosage (milligrams per kilogram per year)
timeFrame: Within 48 weeks after randomization
measure: Change in renal function of the patients
timeFrame: Within 48 weeks after randomization
measure: Change in anthropometry and growth velocity during 48 weeks after randomization
timeFrame: Within 48 weeks after randomization
measure: Change in serum cholesterol, hemoglobin and blood albumin of the patients
timeFrame: Within 48 weeks after randomization
measure: Incidence of infection
timeFrame: Within 48 weeks after randomization
measure: Adverse event
timeFrame: Within 48 weeks after randomization
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
city: Nanjing
country: China
facility: Nanjing Children's Hospital
state: Jiangsu
city: Kunming
country: China
facility: Kunming Children's Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Children's Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Women & Children's Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: Yuying Childrens Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Children's Hospital affiliated to Capital Institute of Pediatrics
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Study officials:
affiliation: Recruiting
name: yi Xie
role: STUDY_DIRECTOR
References:
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citation: Chakraborty R, Mehta A, Nair N, Nemer L, Jain R, Joshi H, Raina R. ACTH Treatment for Management of Nephrotic Syndrome: A Systematic Review and Reappraisal. Int J Nephrol. 2020 Jun 4;2020:2597079. doi: 10.1155/2020/2597079. eCollection 2020.
citation: Lieberman KV, Pavlova-Wolf A. Adrenocorticotropic hormone therapy for the treatment of idiopathic nephrotic syndrome in children and young adults: a systematic review of early clinical studies with contemporary relevance. J Nephrol. 2017 Feb;30(1):35-44. doi: 10.1007/s40620-016-0308-3. Epub 2016 Apr 16.
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citation: Hogan J, Bomback AS, Mehta K, Canetta PA, Rao MK, Appel GB, Radhakrishnan J, Lafayette RA. Treatment of idiopathic FSGS with adrenocorticotropic hormone gel. Clin J Am Soc Nephrol. 2013 Dec;8(12):2072-81. doi: 10.2215/CJN.02840313. Epub 2013 Sep 5.
citation: Zand L, Canetta P, Lafayette R, Aslam N, Jan N, Sethi S, Fervenza FC. An Open-Label Pilot Study of Adrenocorticotrophic Hormone in the Treatment of IgA Nephropathy at High Risk of Progression. Kidney Int Rep. 2019 Oct 31;5(1):58-65. doi: 10.1016/j.ekir.2019.10.007. eCollection 2020 Jan.