Treatment With Octreotide in Patients With Lymphangioleiomyomatosis

Lymphangioleiomyomatosis (LAM), a disease primarily of women of child-bearing age, is characterized by cystic lung disease and abdominal tumors (e.g., angiomyolipomas). Within the LAM patient population is a subset of patients who develop chylous effusions and lymphangioleiomyomas. Treatment of many of these symptoms has been ineffective. Previous studies with somatostatin and octreotide in other clinical settings have shown reduction in chylous effusions. This study assesses the effectiveness of octreotide in symptomatic patients with LAM, lymphangioleiomyomas and/or chylous effusions/ascites, peripheral lymphedema and chyluria.

Study Overview

• Status: Completed
• Conditions: Ascites; Lymphangioleiomyomatosis; Lymphangiomyomas; Pleural Effusions
• Intervention / Treatment: Drug: Octreotide

Detailed Description

Lymphangioleiomyomatosis (LAM), a disease primarily of women of child-bearing age, is characterized by cystic lung disease and abdominal tumors (e.g., angiomyolipomas). Within the LAM patient population is a subset of patients who develop chylous ascites, chylous pleural effusions, chyluria, peripheral lymphedema, and/or lymphangioleiomyomas. Lymphangioleiomyomas are believed to result from a proliferation of abnormal smooth muscle cells within the lymphatic system, which appears to obstruct fluid outflow, leading to fluid accumulation and an increase in size. The lymphangioleiomyomas may occur anywhere along the axial lymphatic chain. In patients with LAM, they occur most frequently in the thorax, abdomen and pelvis and may give rise to a myriad of symptoms (e.g., paresthesias, palpitations, peripheral edema). In some patients, treatment of many of these symptoms, i.e., elevation of lower extremities, paracentesis, thoracentesis, diuretics, and/or surgery, has been ineffective. Previous studies with somatostatin and octreotide in other clinical settings (e.g., traumatic damage to the lymphatics) have shown a successful reduction in chylous effusions, chyluria, ascites, and peripheral lymphedema, when other therapies were less effective. This study will assess the effectiveness of octreotide in symptomatic patients with LAM, lymphangioleiomyomas and/or chylous effusions/ascites, peripheral lymphedema and chyluria. The dose of octreotide starts at 50 micrograms (ug) by the subcutaneous route twice a day. After two weeks the dose will be increased to 200 ug per day and two weeks later to 400 ug/day. Maximal dose is 400 ug twice a day.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

• INCLUSION CRITERIA:

Patients enrolled in the lymphangioleiomyomatosis natural history protocol who have symptoms associated with one of the following:

1. lymphangioleiomyomas
2. chylous pleural effusions
3. peripheral lymph-edema
4. chyloptysis
5. protein-losing enteropathy
6. chyluria

Patients will be included in this protocol if symptoms are attributed to the above processes. Patients with malabsorption disorders, diabetes, hypo/hyperthyroidism, or other endocrine-related disorders will be included if justified clinically based on severity of symptoms.

EXCLUSION CRITERIA:

1. Hypersensitivity to somatostatin, octreotide or its analogues
2. Patients with hepatitis B, hepatitis C, or other clinically significant liver diseases
3. Transplant patients
4. Pregnant women or women who are beast-feeding
5. Patient or another responsible party is unable to give the subcutaneous injection
6. Patient unwilling to be followed per the guidelines set forth
7. Patients with decreased renal function (creatinine greater than 1.5)
8. Patients with HIV infection
9. Immunosuppressed patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Octreotide; Patients with lymphangioleiomyomatosis and lymphatic tumors, ascites or pleural effusions who are symptomatic will receive subcutaneous injections of octreotide starting at a dose of 100 micrograms per day. Doses will be gradually increased to a maximum of 800 micrograms per day, two months after enrollment, if there is no response to lower doses.	Drug: Octreotide; Treatment with octreotide starts at a dose of 50 micrograms(ug) twice a day which is increased to 100 ug twice a day after two weeks and to 200 ug twice a day two weeks later. After two months, if there is no response the dose shall be increased to 400 ug twice a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Reduction in Total Tumor Volume of at Least 20%.	Octreotide treatment will be considered successful if the patient receiving treatment for six months shows a reduction in total tumor mass/ fluid collection or reaccumulation of at least 20%.	Six months
Number of Participants With a Reduction of Pain/Symptoms as Measured by a Simple Numeric Symptom Distress Scale (NDS) to Rate the Severity of Individual Symptoms.	Octreotide treatment will be considered successful if the reported pain/symptom score is reduced by at least 2 levels at termination of treatment. A simple visual numeric distress scale ranging from zero to 10 will be employed to rate the severity of individual symptoms. The best score is zero, which means absence of symptoms and the maximal is 10, meaning that the symptoms are very severe.	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Liver Function Abnormalities	One or more abnormality of the following liver function tests: Alkaline phosphatase above 116 i.u.; SGPT above 41 i.u.; SGOT from 34 i.u.; Total bilirubin above 1.0 mg/dl	Six months

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Ulibarri JI, Sanz Y, Fuentes C, Mancha A, Aramendia M, Sanchez S. Reduction of lymphorrhagia from ruptured thoracic duct by somatostatin. Lancet. 1990 Jul 28;336(8709):258. doi: 10.1016/0140-6736(90)91793-a. No abstract available.

Study record dates

Study Major Dates

• Study Start: June 1, 2000
• Primary Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: June 9, 2000
• First Submitted That Met QC Criteria: June 9, 2000
• First Posted (Estimate): June 12, 2000

Study Record Updates

• Last Update Posted (Estimate): April 30, 2010
• Last Update Submitted That Met QC Criteria: April 29, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: Chylous Ascites; Chylous Pleural Effusion; Inhibitory Effects; Lymphangioleiomyoma; Somatostatin; Lymphangioleiomyomatosis (LAM)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Pleural Diseases; Lymphatic Vessel Tumors; Perivascular Epithelioid Cell Neoplasms; Ascites; Lymphangioleiomyomatosis; Pleural Effusion; Lymphangiomyoma; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: 000147; 00-H-0147 (Other Identifier: NHLBI)