Acromegaly
Conditions
Keywords
Sandostatin LAR
Brief summary
This study aims primarily to determine the effect Insulin-like Growth Factor 1 (IGF-1) normalization into current IGF-I normal ranges with Sandostatin LAR® therapy on biochemical metabolic, cardiovascular and body composition parameters in patients with active acromegaly.
Detailed description
A major goal of treatment of acromegaly is to normalize serum IGF-1 levels. Recently developed new normative data for serum IGF-1 levels has lowered the upper limit of normal for this hormone level. Octreotide, an analog of somatostatin, a synthetic form of the hypothalamic hormone somatostatin, which inhibits growth hormone (GH) release by blocking somatostatin receptors in the pituitary and on the tumor, is now available in a long acting depot formulation, Sandostatin LAR, that suppresses tumoral GH secretion and normalizes GH and IGF-1 levels in about 60% of patients. Although sandostatin LAR is Food and Drug Administration (FDA) approved for the therapy of acromegaly and is used clinically, its efficacy with respect to new normative IGF-1 ranges has not been studied. In addition, an important goal of therapy of acromegaly is to treat co-morbidities of the disease such as insulin resistance, which is common in acromegaly. Other important morbidities in acromegaly are hypertension and cardiovascular disease such as left ventricular hypertrophy (LVH). In this study the investigators will assess the effect of LAR therapy on biochemical parameters as well as important clinical endpoints of therapy of acromegaly.
Interventions
DRUGSandostatin LAR
Open label dose escalation of Sandostatin LAR 10 mg, 20 mg, 30 mg, up to 40 mg if necessary.
Sponsors
Novartis
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults (age \> 18 years) with diagnosis of Acromegaly ( previously confirmed by an elevated IGF-1 level) 2. IGF-1 concentrations\> 10% above the upper limit of normal at screening 3. If the patient have undergone surgical resection of a pituitary adenoma, A minimum of two months must have elapsed post surgery prior to enrollment 4. May have a history of radiotherapy 5. Stable pituitary hormone supplements(x months) prior to baseline visit 6. if female , 1. not pregnant (as evidence by negative serum pregnancy test) or lactating; and 2. If childbearing potential, agree to use a medically acceptable form of contraception (such as oral, implantable, or barrier contraception) from the screening, for the duration of the study, and for at least on month after study discontinuation or completion. Childbearing potential is defined as women who are not surgically sterile or not at least one year postmenopausal. 7. Sign and date an consent form document indicating that the subject (or legally acceptable representative) has been informed of and agrees to all pertinent aspects of trial
Exclusion criteria
1. Have other conditions that may result in abnormal growth hormone (GH) and/or IGF-1 concentrations (e.g., severe hepatic disease, severe renal disease Malnutrition, treatment with levodopa) 2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 x Upper limit of normal or clinically significant hepatic disease 3. Prior somatostatin analog therapy within 6 months of the screening visit 4. Other medical therapy for acromegaly for 6 weeks to screening visit 5. Visual field defects or other neurological symptoms due to tumor mass 6. Have known or suspected drug or alcohol abuse 7. Have received an investigational medication within four week prior to screening or is scheduled to received any investigational medication during the study 8. Do not have ability to fully comprehend the nature of the study, to follow instructions, cooperate with study procedures, and/or are unable to adhere to the visit scheduled outlined in the protocol 9. Have other severe acute or chronic medical or psychiatry condition or Laboratory abnormality that may increase the risk associated with study Participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study 10. Patient who have known hypersensitivity to Sandostatin acetate or other related drug or compound 11. Patient with current gallstones 12. Patient who have received supraphysiologic doses of glucocorticoid within the past 6 months (except for peri-operative (\<3 days duration) of dexamethasone) or who currently received chemotherapeutics agents, or exogenous growth hormone 13. Patients who have received other investigational drugs administered or Received within 30 days of study entry 14. Patients who exhibit symptoms indicative of intolerance during the 2 weeks Course of Sandostatin injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IGF-1 Level on Sandostatin LAR | Up to 9 months | Mean IGF-1 level on treatment with Sandostatin LAR in whole population and responders (normal IGF1) and non responders(elevated IGF-1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular Risk Markers on Sandostatin LAR: C-reactive Protein (CRP) Levels | Up to 9 months | Levels of C-reactive protein (CRP) in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome. |
| Cardiovascular Risk Markers on Sandostatin LAR: Homocysteine Levels | Up to 9 months | Levels of homocysteine in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome. |
| Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Up to 9 months | Levels of lipid panel (cholesterol, triglycerides, and Lipoprotein A) in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label Dose Escalation Study of Sandostatin LAR Therapy Acromegaly is a rare disorder due in almost all cases to a GH secreting tumor of the pituitary gland. The initial treatment is typically surgical removal of the tumor, but after this many patients have residual disease requiring additional therapy. For most patients this therapy is medical with a somatostatin analog.
In addition to biochemical control, important and often overlooked goals of acromegaly care are to treat its associated co-morbidities in particular insulin resistance and diabetes mellitus, hypertension and cardiovascular (CV) disease. Changes in body composition in acromegaly may be integral to the development of insulin resistance and increased CV risk.
Therefore, this study sought to examine the effect of lowering of serum IGF-I levels into the current more stringent normal range during treatment with octreotide LAR on metabolic parameters, body composition and cardiovascular risk profile in patients with acromegaly. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Time constraints | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Open Label Dose Escalation Study of Sandostatin LAR Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 44.9 years |
| IGF-1 Level | 336 ng/ml |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
IGF-1 Level on Sandostatin LAR
Mean IGF-1 level on treatment with Sandostatin LAR in whole population and responders (normal IGF1) and non responders(elevated IGF-1)
Time frame: Up to 9 months
Population: This study was open to adult patients with active acromegaly, either newly diagnosed or failing other therapies who met the following inclusion and exclusion criteria.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Dose Escalation of Sandostatin LAR Therapy | IGF-1 Level on Sandostatin LAR | 336 ng/mL | Standard Deviation 209 |
| Responders | IGF-1 Level on Sandostatin LAR | 186 ng/mL | Standard Deviation 42.4 |
| Non Responders | IGF-1 Level on Sandostatin LAR | 487 ng/mL | Standard Deviation 200.4 |
Comparison: None available.p-value: <0.05t-test, 2 sided
p-value: <0.05t-test, 2 sided
Secondary
Cardiovascular Risk Markers on Sandostatin LAR: C-reactive Protein (CRP) Levels
Levels of C-reactive protein (CRP) in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome.
Time frame: Up to 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Dose Escalation of Sandostatin LAR Therapy | Cardiovascular Risk Markers on Sandostatin LAR: C-reactive Protein (CRP) Levels | 2.05 mg/L | Standard Deviation 3.5 |
| Responders | Cardiovascular Risk Markers on Sandostatin LAR: C-reactive Protein (CRP) Levels | 2.89 mg/L | Standard Deviation 4.79 |
| Non Responders | Cardiovascular Risk Markers on Sandostatin LAR: C-reactive Protein (CRP) Levels | 1.21 mg/L | Standard Deviation 1.2 |
Secondary
Cardiovascular Risk Markers on Sandostatin LAR: Homocysteine Levels
Levels of homocysteine in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome.
Time frame: Up to 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Dose Escalation of Sandostatin LAR Therapy | Cardiovascular Risk Markers on Sandostatin LAR: Homocysteine Levels | 9.98 µmol/L | Standard Deviation 5.8 |
| Responders | Cardiovascular Risk Markers on Sandostatin LAR: Homocysteine Levels | 10.57 µmol/L | Standard Deviation 5.56 |
| Non Responders | Cardiovascular Risk Markers on Sandostatin LAR: Homocysteine Levels | 9.40 µmol/L | Standard Deviation 6.4 |
Secondary
Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels
Levels of lipid panel (cholesterol, triglycerides, and Lipoprotein A) in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome.
Time frame: Up to 9 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Open Label Dose Escalation of Sandostatin LAR Therapy | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Triglycerides | 95.2 mg/dL | Standard Deviation 36.2 |
| Open Label Dose Escalation of Sandostatin LAR Therapy | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | HDL Cholesterol | 52.17 mg/dL | Standard Deviation 14.6 |
| Open Label Dose Escalation of Sandostatin LAR Therapy | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Total cholesterol | 173.75 mg/dL | Standard Deviation 42.9 |
| Open Label Dose Escalation of Sandostatin LAR Therapy | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | LDL cholesterol | 101.56 mg/dL | Standard Deviation 40.7 |
| Open Label Dose Escalation of Sandostatin LAR Therapy | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Lipoprotein a | 55.31 mg/dL | Standard Deviation 68.9 |
| Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | HDL Cholesterol | 53.44 mg/dL | Standard Deviation 16.19 |
| Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Total cholesterol | 182.44 mg/dL | Standard Deviation 49.78 |
| Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | LDL cholesterol | 108.7 mg/dL | Standard Deviation 45.38 |
| Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Triglycerides | 88.38 mg/dL | Standard Deviation 38.13 |
| Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Lipoprotein a | 71.45 mg/dL | Standard Deviation 85.95 |
| Non Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Lipoprotein a | 34.56 mg/dL | Standard Deviation 33.4 |
| Non Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Triglycerides | 103 mg/dL | Standard Deviation 35.1 |
| Non Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | Total cholesterol | 162.57 mg/dL | Standard Deviation 32.1 |
| Non Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | HDL Cholesterol | 50.89 mg/dL | Standard Deviation 13.6 |
| Non Responders | Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels | LDL cholesterol | 92.43 mg/dL | Standard Deviation 34.9 |