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

Phase 4

• Conditions: Peutz-Jeghers Syndrome
• Interventions: Drug: Rapamycin

• Registration Number: NCT03781050
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2018-09-16
• Study First Submitted: 2018-12-06
• Study First Submitted QC: 2018-12-17
• Study First Posted: 2018-12-19
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-18
• Last Update Posted: 2019-01-23
• Primary Completion: 2022-01-01
• Study Completion: 2022-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rapamycin	Rapamycin	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

Primary Outcome Measures

Name	Time	Method
Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps Total load of PJS-related intestinal polyps	The time from start of therapy to 1 year	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Peking Union Medical College Hospital, Chinese Academy of Medicine Sciences; 🇨🇳 Beijing, China/Beijing, China