Ascites, Lymphangioleiomyomatosis, Lymphangiomyomas, Pleural Effusions
Conditions
Keywords
Chylous Ascites, Chylous Pleural Effusion, Inhibitory Effects, Lymphangioleiomyoma, Somatostatin, Lymphangioleiomyomatosis (LAM)
Brief summary
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.
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.
Interventions
DRUGOctreotide
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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Reduction in Total Tumor Volume of at Least 20%. | Six months | 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%. |
| 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. | Six months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Liver Function Abnormalities | Six months | One or more abnormality of the following liver function tests: 1. Alkaline phosphatase above 116 i.u. 2. SGPT above 41 i.u. 3. SGOT from 34 i.u. 4. Total bilirubin above 1.0 mg/dl |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Octreotide Patients with lymphangioleiomyomatosis and lymphatic tumors causing chylous effusions and abdominal pain | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 3 |
Baseline characteristics
| Characteristic | Octreotide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age Continuous | 43 years STANDARD_DEVIATION 5.5 |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 4 |
| serious Total, serious adverse events | 1 / 4 |
Outcome results
Primary
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%.
Time frame: Six months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Octreotide | Number of Participants With a Reduction in Total Tumor Volume of at Least 20%. | 0 Participants | 5 |
Primary
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.
Time frame: Six months
Population: Four patients with lymphangioleiomyomatosis and lymphangioleiomyomas and chylous effusions treated with octreotide injections by the subcutaneous route to determine whether the size of the tumors and effusions decrease with the therapy
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Octreotide | 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. | 1 Participants | 5 |
Secondary
Number of Participants With Liver Function Abnormalities
One or more abnormality of the following liver function tests: 1. Alkaline phosphatase above 116 i.u. 2. SGPT above 41 i.u. 3. SGOT from 34 i.u. 4. Total bilirubin above 1.0 mg/dl
Time frame: Six months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Octreotide | Number of Participants With Liver Function Abnormalities | 1 Participants |