Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome

Study Overview
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Brief Summary
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A prospective non-randomized open label single arm clinical trial to examine the efficacy and safety of sirolimus in patients with Peutz-Jeghers Syndrome.

Detailed Description
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PJS (Peutz-Jeghers Syndrome) is mostly caused by mutations in Lkb1 gene, which leads to an increased activity of mTOR pathway, thus making mTOR inhibitor (sirolimus) a promising candidate in treatment and prevention of PJS. The efficacy of sirolimus (rapamycin) on PJS has been demonstrated in mouse model, but no clinical trials have been reported. Our study was designed as a prospective non-randomized open label single arm clinical trial to examine its efficacy and safety.

Official Title
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Efficacy of Rapamycin (Sirolimus) in the Treatment of Peutz-Jeghers Syndrome

Conditions
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Peutz-Jeghers Syndrome

Intervention / Treatment
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* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients are diagnosed with PJS. Patients have gastrointestinal polyps related syndromes, including abdominal pain, abdominal distension, gastrointestinal bleeding, etc, with imageological examination suggesting intestinal obstruction or intussusception; or whose symptoms recur after previous digestive endoscopic treatment and surgery; or who are inappropriate or unwilling to accept the above treatment again and wish to receive pharmacotherapy. Conventional treatment didn't work well in patients combined with PJS-related tumors. Physical condition (ECGO): 0 3 Organ function is good and biochemical indices meet the following conditions: AST≤2.5×upper limit of normal value (ULN), ALT≤2.5×upper limit of normal value (ULN), Serum total bilirubin (TSB)≤1.5×upper limit of normal value (ULN), Creatinine≤1.5×upper limit of normal value (ULN). No other medications have been received for intestinal polyps within 3 months prior to the clinical trial. Patients participate in the trial voluntarily and have signed the informed consent by the participant or his/her legal guardian. Exclusion Criteria: Patients underwent a surgery within 2 weeks. Patients may need emergency surgery in the near future. Patients are allergic to any ingredient of rapamycin. Patients suffer from a disease requiring immediate blood transfusion. Patients suffer from any disease or condition that may impact implementation of the study or interpretation of the results. This type of diseases includes: Known severe blood coagulation disorders Known anemia that is not caused by intestinal polyps Known hemoglobinopathy Other gastrointestinal infectious diseases Serious heart, liver, kidney and other concomitant diseases that may endanger lives Patients are in pregnancy and lactation. Alcohol or drug (such as aperient) abuse Patients took part in another clinical trial that may influence this study. The researchers believe that there are other unfavorable reasons for the patient to become a subject.
Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycin<br>For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months | Drug: Rapamycin<br>* For children: rapamycin, 1 mg per square meter of body surface area a day, orally, for at least 6 months For adults: rapamycin, 2 mg a day, orally, for at least 6 months<br>* Other names: Sirolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps | Lesion load (cm2) = A+B. A = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by abdomen and pelvis MRI or small bowel CT reconstruction (in cm2). B = sum of the product of maximum diameter and maximum height of the largest 3 lesions shown by digestive endoscope (in cm2). Remarks: 1. If it is impossible to evaluate 3 or more lesions, results of the actual number of lesions should be taken as valid; 2. Lesions evaluated should be correspondent before and after treatment. If the lesion is difficult to assess after treatment, it should be ruled out from the assessment. | The time from start of therapy to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of hemoglobin in blood | The value indicates the amount of gastrointestinal bleeding. | The time from start of therapy to 1 year | 
| Concentration of albumin in blood | The value indicates the status of nutrition. | The time from start of therapy to 1 year | 
| Concentration of hsCRP in blood | The value indicates the level of inflammation. | The time from start of therapy to 1 year | 
| Visual analogue score (VAS) | The value indicates the level of pain. | The time from start of therapy to 1 year | 
| Dermatology life quality index (DLQI) | The value indicates the status of hyperpigmented macules on the lips and oral mucosa. | The time from start of therapy to 1 year | 
| Adverse events | To evaluate safety | The time from start of therapy to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peutz-Jeghers Syndrome (PJS), Rapamycin (sirolimus), Mammalian target of rapamycin (mTOR) inhibitor, Treatment