Acromegaly
Conditions
Keywords
Acromegaly, SERM, Clomiphene
Brief summary
To assess the impact of clomiphene citrate on serum insulin like growth factor 1 and testosterone levels in male acromegalic patients not controlled by surgery, radiotherapy and/or medical treatments (somatostatin analogues, dopamine agonists and/or growth hormone receptor antagonist)
Detailed description
Acromegaly, a disease caused by a growth hormone secreting pituitary adenoma, results in reduced life span. Despite the many modalities available to treat this disease,as surgery, medical treatment and radiotherapy, uncontrolled disease persists in a significant portion of patients Oral estrogens, alone or in combination with somatostatin receptor analogues, have been shown to control acromegaly in women. Selective estrogen receptor modulators (SERMs) resulted in similar effects in both genders. Clomiphene citrate, a SERM that increases luteinizing hormone and follicle stimulating hormone secretion, improves hypogonadism and fertility outcomes. The aim of this study is to assess the impact of clomiphene citrate on serum insulin like growth factor 1 and testosterone levels in male acromegalic patients not controlled by surgery, radiotherapy and/or medical treatment. In this prospective, open label, single center trial, sixteen male patients were studied. Clomiphene citrate (50 mg/day) was added to previous medical treatment for 3 months and hormonal assessment was performed prior to and during the intervention. Hormones included: growth hormone, insulin like growth factor, total testosterone, follicle stimulating hormone, luteinizing hormone and prostate-specific antigen.
Interventions
DRUGClomiphene Citrate
Clomiphene citrate, 50 mg, orally for three months
Sponsors
Felipe Henning Gaia Duarte
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* patients with active acromegaly on regular use of a stable dose of Octreotide-LAR and/or cabergoline for at least one year, * Insulin like growth factor 1 above the reference range during the last year of follow-up and * testosterone levels within or below the third inferior tertile of normality.
Exclusion criteria
* radiotherapy in the last 10 years, previous venous embolism (including family members), * previous prostatic cancer or symptomatic benign hypertrophy, * triglyceride levels above 400 mg/dL, * renal failure defined by estimative of renal filtration below 30 ml/min, * liver disease defined by hepatic enzymes 3 times above normal limit, * active oncologic disease in the last 10 years and previous cardiac or cerebrovascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IGF-1 Levels | Day 90 | The objective is to compare the change of IGF-1 value assessed in the beginning of the study (day 0), with the value obtained after three months of use of clomiphene citrate (day 90). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Testosterone Levels | D90 | The objective is to compare the change of testosterone value assessed in the beginning of the study (day 0), with the value obtained after three months of use of clomiphene citrate (day 90). |
| PSA Levels | Day 90 | The objective is to compare the change of PSA value assessed in the beginning of the study (day 0), with the value obtained after three months of use of clomiphene citrate (day 90). |
Participant flow
Recruitment details
Acromegalic patients with uncontrolled hormonal levels despite current medical treatment
Pre-assignment details
Patients should be on stable medical treatment for at least 6 months prior entering the study. Patients submitted to radiotherapy in the last 10 years were not eligible.
Participants by arm
| Arm | Count |
|---|---|
| Clomiphene Citrate Patients receiving clomiphene citrate Clomiphene Citrate: Clomiphene citrate, 50 mg, orally for three months
Patients with active acromegaly, defined by high IGF-1 levels, on regular use of a stable dose of Octreotide-LAR and/or Cabergoline for at least 1 year; IGF-1 above the reference range during the last year of follow-up; and T levels within or below the third inferior tertile of normality. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Three Months of Clomiphene Wash-out | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Clomiphene Citrate |
|---|---|
| Age, Customized | 52.5 years |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
IGF-1 Levels
The objective is to compare the change of IGF-1 value assessed in the beginning of the study (day 0), with the value obtained after three months of use of clomiphene citrate (day 90).
Time frame: Day 90
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clomiphene Citrate | IGF-1 Levels | 424 ng/mL | Standard Deviation 108 |
Comparison: Measures of central tendency (mean) and variability (range and/or SD) were used to describe numeric variables. Paired Student's t test was used to verify the mean differences between dependent normally distributed variables. Wilcoxon sign test was performed to non-normally distributed dependent variables.~Asignificance level of 5%was adopted for all statistical tests (P \<.05).p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary
PSA Levels
The objective is to compare the change of PSA value assessed in the beginning of the study (day 0), with the value obtained after three months of use of clomiphene citrate (day 90).
Time frame: Day 90
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Clomiphene Citrate | PSA Levels | 2.0 ng/mL | Standard Deviation 2 |
Secondary
Testosterone Levels
The objective is to compare the change of testosterone value assessed in the beginning of the study (day 0), with the value obtained after three months of use of clomiphene citrate (day 90).
Time frame: D90
Population: 10 acromegalic patients were assessed, the other 6 patients did not have testosterone levels assessed.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Clomiphene Citrate | Testosterone Levels | 282 ng/dL | Standard Deviation 210 |