Anastrazole and Clomiphene to Evaluate Hypogonadal Symptoms and Erectile Function (CAP)

A Randomized Double Blinded Placebo Controlled Trial Between Anastrozole and Clomiphene to Evaluate Improvement in Hypogonadal Symptoms and Erectile Function Using ADAM, IIEF and EHS Validated Scales

This study evaluates anastrazole and clomiphene in the improvement in hypogonadal symptoms and erectile function. Each subject will receive Anastrazole 1 mg/day, clomiphene 25 mg/day and placebo in randomized schedule of 8 week intervals.

Study Overview

• Status: Completed
• Conditions: Hypogonadism, Male
• Intervention / Treatment: Drug: Anastrozole 1mg; Drug: Clomiphene Citrate 25mg; Drug: Placebo - Cap

Detailed Description

Aromatase inhibitors (AI) (Anastrazole) and selective estrogen receptor modifiers (SERMS)(clomiphene) increase testosterone production through stimulation of the hypothalamic pituitary axis. While these drugs both reduce the feedback inhibition of estrogen on the pituitary, SERMs cause an increase in serum estradiol, whereas AIs reduce estradiol levels. Using these medications, we can obtain therapeutic testosterone levels with either an increase or decrease in estradiol levels.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Men age 18-70
2. Baseline morning Testosterone 150-350 ng/dL x2
3. leutenizing hormone (LH) 1.5-9.2 miU/mL, Follicle stimulation hormone (FSH) 1.6-8.0 miU/mL, Prolactin 4-15 ng/mL
4. Positive Androgen Deficiency in the Aging Male (ADAM) score. A positive score is when an affirmative answer (''yes'') to either questions "Do you have a decreased sex drive/libido?" or "Are your erections less strong?" or any three other questions.10
5. Body mass index (BMI) <40
6. Sexual health inventory for men (SHIM) score >7 and <21. Patients are allowed to be taking phosphodiesterase 5 inhibitors (i.e. Viagra, Levitra, Cialis) at baseline, however we will ask them to do the SHIM survey as if they were not taking this medication.
7. Men must attempt to have at least four sexual encounters over each of the eight-week periods
8. Men willing not to take phosphodiesterase 5 inhibitors throughout the entire study

Exclusion Criteria:

1. Current or previous history of prostate cancer
2. Previous or current androgen deprivation therapy for prostate cancer,
3. Past surgical history of prostatectomy.
4. History of testicular cancer.
5. History of deep vein thrombosis (DVT) or blood dyscrasia
6. History of breast cancer
7. Men with past or current treatment for erectile dysfunction including MUSE (alprostodil), intracavernosal injections, penile prosthesis. Men not on treatment or men who are on phosphodiesterase inhibitors will be allowed to be in the study but must stop their use at the screening visit.
8. Chronic opioid use
9. Use of steroids within the past 3 months, including prednisone and/or cortisone injections, and inhaled steroids. Topical steroid cream is acceptable.
10. History of or current use of anabolic steroids, i.e. testosterone, (or any analog of testosterone) dihydroepiandrosterone (DHEA), dihydroepiandrosterone sulfate (DHEAS) or any growth promoters i.e. growth hormone itself or analogs of growth hormone
11. History of or current use of anti-androgen medications, i.e. Aldactone, Tagamet, estrogens
12. Alcohol intake > 30 grams (drink more than 2 beers per day OR more than 1 glass of wine or cocktail daily)
13. Having started a new medication during the past three months which may interfere with the outcome measures of the study
14. Polycythemia (HCT >52% )
15. History of prostate specific antigen (PSA)> 4.0 ng/dl
16. Hematocrit (HCT)< 36 %
17. Liver function tests greater than 2 times upper normal limits or history of abnormal electrolytes, calcium or Parathyroid hormone without workup, at the discretion of the investigator.
18. Previous hypogonadal treatment within last 3 months. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: anastrazole-clomiphene-placebo; anastrozole for eight weeks then clomiphene for eight weeks then placebo for eight weeks	Drug: Anastrozole 1mg; Drug: Clomiphene Citrate 25mg; Drug: Placebo - Cap
Other: anastrazole-placebo-clomiphene; anastrozole for eight weeks then placebo for eight weeks then clomiphene for eight weeks	Drug: Anastrozole 1mg; Drug: Clomiphene Citrate 25mg; Drug: Placebo - Cap
Other: clomiphene-anastrazole-placebo; clomiphene for eight weeks then anastrozole for eight weeks then placebo for eight weeks	Drug: Anastrozole 1mg; Drug: Clomiphene Citrate 25mg; Drug: Placebo - Cap
Other: clomiphene-placebo-anastrazole; clomiphene for eight weeks then placebo for eight weeks then anastrozole for eight weeks	Drug: Anastrozole 1mg; Drug: Clomiphene Citrate 25mg; Drug: Placebo - Cap
Other: placebo-clomiphene-anastrazole; placebo for eight weeks then clomiphene for eight weeks then anastrozole for eight weeks	Drug: Anastrozole 1mg; Drug: Clomiphene Citrate 25mg; Drug: Placebo - Cap
Other: placebo-anastrazole-clomiphene; placebo for eight weeks then anastrozole for eight weeks then clomiphene for eight weeks	Drug: Anastrozole 1mg; Drug: Clomiphene Citrate 25mg; Drug: Placebo - Cap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IIEF (International Index of Erectile Function) Score - Screen	15 item self reported erectile function. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75	At baseline
IIEF (International Index of Erectile Function) Score - Week 8	15 item self reported erectile function over the past 8 weeks. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75	Week 8
IIEF (International Index of Erectile Function) Score - Week 16	15 item self reported erectile function over the past 8 weeks. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75	Week 16
IIEF (International Index of Erectile Function) Score - Week 24	15 item self reported erectile function over the past 8 weeks. Each item is scored 0-5 with 0=negative response and 5 = positive response with totals of 0-75	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalized Testosterone - Screen	Normalized at >350ng/dl	Baseline
Normalized Testosterone - Week 8	Normalized at >350ng/dl	Week 8
Normalized Testosterone - Week 16	Normalized at >350ng/dl	Week 16
Normalized Testosterone - Week 24	Normalized at >350ng/dl	Week 24
ADAM (Androgen Deficiency in the Aging Male) Score - Screen	Self reported quantification of hypogonadism. 10 "yes" or "no" questions. A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions. Yes (1) represents a better outcome than No (1) In Data Entry: Yes - 1 No - 0	Baseline
ADAM (Androgen Deficiency in the Aging Male) Score - Week 8	Self reported quantification of hypogonadism. 10 "yes" or "no" questions. A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions. Yes (1) represents a better outcome than No (1) In Data Entry: Yes - 1 No - 0	Week 8
ADAM (Androgen Deficiency in the Aging Male) Score - Week 16	Self reported quantification of hypogonadism. 10 "yes" or "no" questions. A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions. Yes (1) represents a better outcome than No (1) In Data Entry: Yes - 1 No - 0	Week 16
ADAM (Androgen Deficiency in the Aging Male) Score - Week 24	Self reported quantification of hypogonadism. 10 "yes" or "no" questions. A positive (yes) questionnaire result is defined as a "yes or 1" and a negative (no) questionnaire result is defined as a "no or 0" to question 1 or question 7 or any 3 other questions. Yes (1) represents a better outcome than No (1) In Data Entry: Yes - 1 No - 0	Week 24
EHS (Erectile Hardness Score) - Screen	Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid	Baseline
EHS (Erectile Hardness Score) - Week 8	Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid	Week 8
EHS (Erectile Hardness Score) - Week 16	Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid	Week 16
EHS (Erectile Hardness Score) - Week 24	Self reported questionnaire rated 0-4 0=penis does not enlarge, 4=Penis completely hard and fully rigid	Week 24
LH - Screen	Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.	Baseline
LH - Week 8	Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.	Week 8
LH - Week 16	Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.	Week 16
LH - Week 24	Luteinizing Hormone levels collected at the initial encounter and at the end of the 8, 16, and 24 week periods.	Week 24
FSH - Screen	Lab Values for follicle stimulating hormone	Baseline
FSH - Week 8	Lab Values for follicle stimulating hormone	Week 8
FSH - Week 16	Lab Values for follicle stimulating hormone	Week 16
FSH - Week 24	Lab Values for follicle stimulating hormone	Week 24
Free Testosterone - Screen	Measure of Free Testosterone	Baseline
Free Testosterone - Week 8	Measure of Free Testosterone	Week 8
Free Testosterone - Week 16	Measure of Free Testosterone	Week 16
Free Testosterone - Week 24	Measure of Free Testosterone	Week 24
Estradiol - Screen	Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24	Baseline
Estradiol - Week 8	Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24 An entered value of 4.9 means the measure was <5	Week 8
Estradiol - Week 16	Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24 An entered value of 4.9 means the measure was <5	Week 16
Estradiol - Week 24	Measurement of Estradiol levels at initial encounter and at the end of Weeks 8, 16, and 24 An entered value of 4.9 means the measure was <5	Week 24
SHBG - Screen	Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24	Baseline
SHBG - Week 8	Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24	Week 8
SHBG - Week 16	Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24	Week 16
SHBG - Week 24	Lab Measure of sex hormone binding globulin at the initial encounter and at the ends of week 8, 16, and 24	Week 24
SEP #1-3 Cumulative - Screen	Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3. 0-3: cumulative score from SEP questions 1, 2, and 3 Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0	Baseline
SEP #1-3 Cumulative - Week 8	Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3. 0-3: cumulative score from SEP questions 1, 2, and 3 Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0	Week 8
SEP #1-3 Cumulative - Week 16	Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3. 0-3: cumulative score from SEP questions 1, 2, and 3 Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0	Week 16
SEP #1-3 Cumulative - Week 24	Questions 1, 2, and 3 for the Sexual Encounter Profile have been cumulatively added. 1 - yes and 0 - no have been added for questions 1-3 to determine a total value from 0-3. 0-3: cumulative score from SEP questions 1, 2, and 3 Higher values (3) are considered to be a better outcomes relative to lower numbers (0) 3 is better than 2 is better than 1 is better than 0	Week 24

Collaborators and Investigators

• Sponsor: Albany Medical College
• Collaborators: Laboratory Corporation of America
• Investigators: Principal Investigator: Robert C Welliver, MD, Albany Medical College

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2015
• Primary Completion (Actual): March 8, 2017
• Study Completion (Actual): March 8, 2017

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: April 29, 2019
• First Posted (Actual): May 1, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: October 26, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Eunuchism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Anastrozole; Clomiphene; Enclomiphene; Zuclomiphene
• Other Study ID Numbers: 4134 (Other Identifier: Stanford IRB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No