Hydrocortisone Treatment for Symmetric Lipomatosis Associated With Neuropathy (SLN): an N-of-1 Study Hydrocortisone Treatment for Symmetric Lipomatosis Associated With Neuropathy (SLN): an N-of-1 Study

Study Overview
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Brief Summary
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A young women with Symmetric Lipomatosis associated with Neuropathy (SLN) was seen at the department of Internal Medicine - Endocrinology and at the department of Neurology at the Erasmus MC, Rotterdam, the Netherlands. The patient presented with balance problems due to neuropathy and prominent cervical and genital lipomas. In the past, the patient had been treated with steroids for a short period. The patient noticed that, as a 'side effect', during this treatment period the lipomas shrank and that the balance problems nearly disappeared. The complaints reappeared after withdrawal of the steroids. In the current study, the usefulness of steroid treatment in this single patient will be investigated in an N-of-1 trial. Primary objective: to determine the efficacy of hydrocortisone treatment for neuropathy on an individual level in a patient with SLN as assessed with the Rasch-built Overall Disability Scale (RODS).

Detailed Description
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A young women with Symmetric Lipomatosis associated with Neuropathy (SLN) was seen at the department of Internal Medicine-Endocrinology and the department of Neurology at the Erasmus MC, Rotterdam, the Netherlands. SLN is a rare disorder characterized by symmetric lipomas and neuropathy due to a homozygous mutation of c.2119C>T p.R707W in the MFN2 gene. Only seven cases of SLN are known in the literature. The patient presented with balance problems due to neuropathy and prominent cervical and genital lipomas. In the past, the patient had been treated with steroids (prednisolone) for a short period, because of a suspicion of adrenal insufficiency. The patient noticed that, as a 'side effect', during this treatment period the lipomas shrank and that the balance problems nearly disappeared. However, as a synacthen test showed that adrenal function was normal, steroid treatment was tapered and the complaints reappeared. In a follow-up visit at our outpatient clinic, the patient requested to be treated again with steroids for the complaints. As there is no literature on the effects of treatment with steroids on balance problems and on the size of lipomas in patients with SLN, the usefulness of steroid treatment in this single patient is investigated in an N-of-1 trial in order to improve the clinical care for this patient. Primary objective: to determine the efficacy of hydrocortisone treatment for neuropathy on an individual level in a patient with SLN as assessed with the Rasch-built Overall Disability Scale (RODS). Secondary objectives: to determine the effect of hydrocortisone treatment on the size of a lipoma in the neck, on the Medical Research Council (MRC) sum score and on specific personalized goals that are important to the patient and the patients' environment (Goal Attainment Scaling (GAS)).

Official Title
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Hydrocortisone Treatment for Symmetric Lipomatosis Associated With Neuropathy (SLN): an N-of-1 Study

Conditions
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Symmetric Lipomatoses, Multiple

Intervention / Treatment
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* Drug: Hydrocortisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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The study is especially designed for a specific female patient. The patient is 31 years old at the moment. Since the study is especially designed for this patient, there are no formal inclusion and exclusion criteria. However, the study will be stopped when the patient gets pregnant as this can influence the primary and secondary outcome measures. Inclusion Criteria: N/A Exclusion Criteria: Pregnancy

Ages Eligible for Study
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Minimum Age: 31 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: An N-of-1 study is considered as a reliable and suitable design to assess the efficacy of a treatment at an individual level. The study will consist of two cycles with each two periods of active treatment or placebo, a run-in period, tapering period and a wash-out period. Within each cycle, the sequence of the hydrocortisone and placebo period is randomized.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrocortisone<br>Hydrocortisone (20 mg/day) in a 10-5-5 schedule: 10 mg at 0700h, 5 mg at 1200h, and 5 mg at 1700h. The hydrocortisone periods last 10 weeks per period. In total, there are two hydrocortisone periods. | Drug: Hydrocortisone<br>* Hydrocortisone is orally administered.<br>|
| Placebo Comparator: Placebo<br>Placebo (20 mg/day) in a 10-5-5 schedule: 10 mg at 0700h, 5 mg at 1200h, and 5 mg at 1700h. The placebo periods last 10 weeks per period. In total, there are two placebo periods. | Drug: Placebo<br>* Placebo is orally administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rasch-built Overall Disability Scale (RODS) | The RODS is a validated 24-items questionnaire to measure the activity and social participation limitations in patients with neuropathy. The questionnaire has a score range of 0 to 100. A higher score means a better outcome (less limitations of the neuropathy) | Baseline to 414 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Size of lipoma | The size of the lipoma will be measured with a centimeter by the researcher during hospital visits. The researcher will also take a picture of the lipoma in front of graph paper in a standardized manner. In between hospital visits, the participant will take a picture of the lipoma in front of graph paper. | Baseline to 414 days | 
| Medical Research Council (MRC) sumscore | The MRC sumscore is a validated tool to measure muscle strength and must be carried out by a physician, nurse, physiotherapist or other professional. The score has a range of 1 to 5. A higher score means a better outcome. | Baseline to 414 days | 
| Goal Attainment Scaling (GAS) | GAS is an individualized outcome measure in which several personal goals and the corresponding scaling are defined in consultation with the patient. The scaling is standardized, which makes it possible to reliably measure the change in the situation of the patient. The levels range from -3 to +2. A higher level means a better outcome. The predefined personal goals are a measure of the effectivity of the treatment. If possible, three goals will be set. | Baseline to 414 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Symmetric Lipomatosis associated with Neuropathy, Hydrocortisone, Neuropathy, Lipoma