Aromatase Inhibitor Growth Study: Letrozole vs. Anastrozole

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02137538
• Collaborator: (none)
• Enrollment: 79
• Location: 1
• Arms: 2
• Actual Duration (Months): 102.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of the study is to determine if there are differences in the final height or hormone profile of short pubertal boys placed on different forms of aromatase inhibitor now routinely used to increase stature: Anastrozole and Letrozole. It also should determine if there are differences in the side effect profiles of the two drugs to be used.

Condition or Disease	Intervention/Treatment	Phase
Short Stature	Drug: Letrozole; Drug: Anastrozole	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomization to Letrozole vs. Anastrozole in Short Pubertal Males
• Actual Study Start Date: Nov 18, 2009
• Actual Primary Completion Date: Jun 5, 2018
• Actual Study Completion Date: Jun 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Letrozole Letrozole 2.5 mg daily	Drug: Letrozole
Active Comparator: Anastrozole Anastrozole 1 mg daily	Drug: Anastrozole

Outcome Measures

Primary Outcome Measures

1. Predicted Adult Height at Year 3 [Year 3]

   Heights will be obtained by physical exam every 6 months during treatment. Skeletal maturation will be assessed from an x-ray by the method of Greulich and Pyle at baseline and every 12 months until the end of treatment. Predicted adult height will be calculated at baseline and at the end of treatment based upon measured height and skeletal maturation (bone age).

Secondary Outcome Measures

1. Serum Testosterone [Baseline, year 3]

2. Dihydrotestosterone [Baseline, year 3]

3. Androstenedione [Baseline, year 3]

4. Luteinizing Hormone [Baseline, year 3]

5. Follicle Stimulating Hormone [Baseline, year 3]

6. Insulin-like Growth Factor Type 1 [Baseline, year 3]

7. Inhibin B [Baseline, year 3]

8. Estradiol [Baseline, year 3]

9. Estrone [Baseline, year 3]

10. Number of Adverse Events Related to Acne or Bone Fracture [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current height less than 5th percentile AND/OR

• Predicted adult height (based on bone age) more than 10 cm below target height (mid parental height)

• Evidence of puberty: physical signs and serum luteinizing hormone > 0.3 IU/L and testosterone > 15 ng/dl

Exclusion Criteria:

• Bone age reading more than 14.0 years

• Follicle stimulating hormone > 20 IU/L

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lucile Packard Children's Hospital	Palo Alto	California	United States	94301

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: E Kirk Neely, MD, Stanford University
• Principal Investigator: Laura K Bachrach, MD, Stanford University
• Principal Investigator: Walter A Zegarra, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol - Mar 26, 2019
• Statistical Analysis Plan - Jun 24, 2021

More Information

Publications

None provided.

• Responsible Party: Laura K Bachrach, Professor of Pediatrics, Stanford University
• ClinicalTrials.gov Identifier: NCT02137538
• Other Study ID Numbers: AI growth study
• First Posted: May 14, 2014
• Last Update Posted: Jul 15, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Dwarfism; Letrozole; Anastrozole

Study Results

Participant Flow

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Period Title: Overall Study
STARTED	39	40
COMPLETED	23	26
NOT COMPLETED	16	14

Baseline Characteristics

Arm/Group Title	Letrozole	Anastrozole	Total
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily	Total of all reporting groups
Overall Participants	30	35	65
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.9 (1.2)	13.9 (1.5)	13.9 (1.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	30 100%	35 100%	65 100%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	30 100%	35 100%	65 100%
Bone age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	156.1 (6.6)	156.3 (12.2)	156.2 (9.9)
Predicted Adult Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	167.2 (5.8)	167.3 (6.9)	167.2 (6.4)

Outcome Measures

1. Primary Outcome

Title	Predicted Adult Height at Year 3
Description	Heights will be obtained by physical exam every 6 months during treatment. Skeletal maturation will be assessed from an x-ray by the method of Greulich and Pyle at baseline and every 12 months until the end of treatment. Predicted adult height will be calculated at baseline and at the end of treatment based upon measured height and skeletal maturation (bone age).
Time Frame	Year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Mean (Standard Deviation) [cm]	167.8 (5.8)	169.4 (5.1)

2. Secondary Outcome

Title	Serum Testosterone
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	213.1 (133.7)	162.1 (124.6)
Year 3	882.3 (250.5)	680.1 (179.5)

3. Secondary Outcome

Title	Dihydrotestosterone
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	22.5 (11.3)	19.1 (9.7)
Year 3	65.0 (20.2)	44.1 (23.5)

4. Secondary Outcome

Title	Androstenedione
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	35.3 (13.1)	37.4 (21.4)
Year 3	79.9 (21.5)	77.9 (28.2)

5. Secondary Outcome

Title	Luteinizing Hormone
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	2.3 (1.5)	1.8 (1.1)
Year 3	4.7 (1.9)	3.4 (2.0)

6. Secondary Outcome

Title	Follicle Stimulating Hormone
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	3.3 (1.9)	2.5 (1.3)
Year 3	6.6 (2.4)	4.5 (2.9)

7. Secondary Outcome

Title	Insulin-like Growth Factor Type 1
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	306.2 (112.8)	306.9 (112.9)
Year 3	226.1 (54.4)	298.7 (78.8)

8. Secondary Outcome

Title	Inhibin B
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	203.4 (55.0)	217.0 (65.2)
Year 3	257.6 (61.1)	262.1 (97.9)

9. Secondary Outcome

Title	Estradiol
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	4.9 (3.6)	4.7 (4.7)
Year 3	2.7 (2.1)	6.2 (2.5)

10. Secondary Outcome

Title	Estrone
Time Frame	Baseline, year 3

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Baseline	8.7 (4.8)	8.0 (4.9)
Year 3	2.7 (0.3)	3.5 (3.2)

11. Secondary Outcome

Title	Number of Adverse Events Related to Acne or Bone Fracture
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Participants who finished the first year of therapy are included in the analysis, excluding participants who had received growth hormone.

Arm/Group Title	Letrozole	Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily	Participants receive anastrozole 1 mg daily
Measure Participants	30	35
Acne	3	3
Fracture	3	5

Adverse Events

Time Frame	3 years
Arm/Group Title	Letrozole		Anastrozole
Arm/Group Description	Participants receive letrozole 2.5 mg daily		Participants receive anastrozole 1 mg daily
All Cause Mortality
	Letrozole		Anastrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/40 (0%)
Serious Adverse Events
	Letrozole		Anastrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		2/40 (5%)
Musculoskeletal and connective tissue disorders
Sacroiliitis	0/39 (0%)	0	1/40 (2.5%)	1
Nervous system disorders
Neuro event	0/39 (0%)	0	1/40 (2.5%)	1
Other (Not Including Serious) Adverse Events
	Letrozole		Anastrozole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/39 (30.8%)		10/40 (25%)
Injury, poisoning and procedural complications
Fracture	3/39 (7.7%)	3	4/40 (10%)	5
Musculoskeletal and connective tissue disorders
Scoliosis	1/39 (2.6%)	1	2/40 (5%)	2
Nervous system disorders
Aggression	1/39 (2.6%)	1	0/40 (0%)	0
Skin and subcutaneous tissue disorders
Acne	3/39 (7.7%)	3	3/40 (7.5%)	3
Hair loss	4/39 (10.3%)	4	1/40 (2.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.