Clomiphene Citrate for Treatment of Acromegaly

Clomiphene Citrate for Treatment of Acromegaly Not Controlled by Conventional Therapies

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)

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: Clomiphene Citrate

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

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: Clomiphene citrate; Patients receiving clomiphene citrate	Drug: Clomiphene Citrate; Clomiphene citrate, 50 mg, orally for three months; Other Names: Clomid; Serophene; Indux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	D90
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).	Day 90

Collaborators and Investigators

• Sponsor: Felipe Henning Gaia Duarte
• Investigators: Study Chair: Marcello D Bronstein, MD, PhD, Unit of Neuroendocrinology, Discipline of Endocrinology, Department of Internal Medicine Clinical Hospital of the University of São Paulo Medical School, São Paulo, Brazil

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: October 20, 2014
• First Submitted That Met QC Criteria: October 23, 2014
• First Posted (Estimate): October 24, 2014

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Acromegaly; Clomiphene; SERM
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Acromegaly; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: ClomipheneAcro