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CompletedNCT00957528Updated Sep 10, 2012Results posted

Cycled Testosterone Replacement Study

A Phase 1 interventional study of Testosterone and Placebo in Hypogonadism, sponsored by The University of Texas Medical Branch, Galveston. Completed at 1 site in United States. Open to male participants aged 60 Years to 85 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2012-09-10.

Sponsored by The University of Texas Medical Branch, Galveston · Phase 1, Interventional, and Prevention

Phase
Phase 1
Study type
Interventional
Enrollment
26
Allocation
Randomized
Ages
60 Years to 85 Years
Sex
Male
01

Study summary

The purpose of this study is to determine whether testosterone (male hormone) therapy is effective if administered in a cyclic fashion (periodic dosing) compared to continuous dosing in men aged 60 to 85 years. Effectiveness will be determined based on improvements in body composition, muscle metabolism, muscle strength, and bone metabolism.

Read the detailed description

Men and women undergo a progressive reduction in lean muscle mass (sarcopenia) with advancing age regardless of their level of physical activity. A 12-yr longitudinal study in healthy sedentary older men showed a correlation between loss of muscle cross-sectional area and muscle strength of the thigh, quadriceps, and flexor muscles. Once weakened, older individuals are prone to falls that prevent independent living and diminish the quality of life. There is a need to develop therapies to counteract losses in skeletal muscle strength with aging. Studies show that exercise and testosterone administration increase skeletal muscle mass and strength in older men. However, the increase in muscle strength by testosterone in older men has not been consistent in all studies. Androgens increase muscle mass by either increasing muscle protein synthesis or inhibiting muscle protein breakdown. This proposal will investigate the hypothesis that cyclic testosterone administration (monthly on/off cycles) will preferentially increase muscle protein synthesis and result in a consistent and greater improvement in muscle strength than continuous testosterone administration.

02

Conditions studied

  • Hypogonadism

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Keywords

  • Low Normal Testosterone
  • Male
  • Aging
03

In context

Hypogonadism

352 studies on the registry are indexed under Hypogonadism; 44 are open to participants now.

This study's enrollment of 26 is below the median of 55 across 265 interventional studies indexed under Hypogonadism.

Browse Hypogonadism studies →

Lead sponsor

The University of Texas Medical Branch, Galveston is the lead sponsor of 256 studies on the registry; 39 are open to participants now.

Of its 32 completed or terminated interventional studies of FDA-regulated products, 26 (81%) have results posted.

Browse The University of Texas Medical Branch, Galveston studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
60 Years to 85 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Availability of transportation (i.e., subjects must be able to provide their own transportation to UTMB).

Exclusion criteria

Exclusion Criteria:

  • Medications such as anticoagulants (Coumadin) and glucocorticoids.
  • History of angina that occurs with exertion or at rest.
  • History of myocardial infarction within the last 12 months.
  • Failure to successfully complete an exercise stress test using the Bruce protocol. Subjects that demonstrate ≥ 0.1 mV horizontal or downsloping ST segment depression, a drop in systolic blood pressure of ≥ 10 mm Hg, and/or frequent or repetitive arrhythmias (defined as ≥ 10 PVC/min, or couplets) during the stress test will be excluded.
  • LDL cholesterol above 200 mg/dL.
  • History of prostatic cancer.
  • Elevated prostate specific antigen (PSA) above 4.0 µg/L, or severe benign prostatic hypertrophy (BPH) by history (frequent urination, reduced stream).
  • Serum total testosterone concentrations of greater than 500 ng/dL.
  • Subjects who engage in high intensity, elite training on a regular basis.
  • Major medical illness such as diabetes, chronic obstructive pulmonary disease, or sleep apnea.
  • Recent history of smoking tobacco.
  • Hematocrit greater than 51%.
  • Morbidly obese older men (BMI > 35).
  • Hypertension: Blood pressure on three consecutive measurements taken at one week intervals that has a systolic pressure ≥ 140 or a diastolic blood pressure ≥ 90. Subjects will be included if they are on two or less blood pressure medications and have a blood pressure below these criteria.
  • History of hepatitis or a 3-fold elevation of liver function tests (Alk phos, ALT, AST).
  • Bone related disorders such as osteoporosis or parathyroid disease.
  • DEXA scans revealing lumbar spine T-scores of less than -2.5.
  • Subjects currently taking anti-bone-resorptive agents such as bisphosphonates, parathyroid hormone, or calcitonin.
05

Study design

Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
26 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Weekly placebo treatment for a duration of 5 months.

    Drug: Placebo

  • Experimental
    Monthly Cycled Testosterone

    A month of weekly testosterone treatment alternated by a month of weekly placebo treatment for a duration of 5 months.

    Drug: Testosterone · Drug: Placebo

  • Experimental
    Continuous Testosterone

    Weekly testosterone treatment for a duration of 5 months

    Drug: Testosterone

Interventions

  • DrugTestosterone

    Weekly im injections of 100 mg testosterone enanthate.

    Also known as: Testosterone Enanthate

  • DrugPlacebo

    Weekly IM injections of sesame oil.

    Also known as: Sesame Oil

06

What researchers measure

Primary outcomes

  1. Changes in Basal Muscle Protein Synthesis and Breakdown as Measured by Stable Isotope Metabolic Studies at Baseline and at Five Months

    The fractional synthetic rate (FSR) of mixed muscle is calculated by directly measuring the incorporation of L-\[ring-13C6\]-phenylalanine into protein (%/hr),, using the precursor-product model: FSR = \[(EP2 - EP1)/(EM•t)\]•60•100, where EP1 and EP2 are the enrichments of bound L-\[ring-13C6\]-phenylalanine in the first and second muscle biopsies, t is the time interval (min) between biopsies, and EM is the mean L-\[ring-13C6\]-phenylalanine enrichment in the muscle intracellular pool.

    Time frame: 5 Months

  2. Changes in Muscle Strength as Measured by Maximal Voluntary Contraction Tests (Arm Curl) at Baseline, One Month, Two Months, Three Months, Four Months, and at Five Months

    Maximum weight (pounds) lifted using Cybex weight machine in a single effort(1-RM) for upper extremities (biceps and triceps) and lower extremities quadriceps and hamstrings).

    Time frame: 5 months

  3. Changes in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA)

    Lean body mass is expressed in grams as calculated by Hologic DEXA.

    Time frame: 5 months

Secondary outcomes

  1. Changes in Bone Mineral Density as Measured by Dual Energy X-ray Absorptiometry (DEXA)

    Bone mineral density measure by measured by dual energy x-ray absorptiometry (DEXA)measured at baseline and a five months

    Time frame: 5 months

  2. Changes in Serum Markers of Bone Turnover.

    Measures of bone turnover markers in serum samples at baseline and at five months.The bone turnover markers analyzed include: Markers associated with bone breakdown NTX (N-telopeptide) TRAP5b (tartrate-resistant acid phosphatase isoform 5b) Markers associated with bone formation Osteocalcin BAP (bone specific alkaline phosphatase) Regulators of bone formation iPTH (intact parathyroid hormone) increases in response to bone loss Calcitonin inhibits bone formation in response to elevated levels of serum calcium

    Time frame: 5 months

  3. 9473Changes in Serum Inflammatory Biomarkers and Muscle Inflammatory Cytokines

    Serum inflammatory biomarkers (Interleukin B-1, 2,5,6,7,8,10,12 13, Interferon gamma, GM-CSF, and Tumor Necrosis Factor alpha)as measured by immunoassay at baseline and at five months

    Time frame: 5 months

07

Results

Posted Aug 21, 2012

Participant flow

Subject recruitment began in January, 2006 and was closed on December, 2011. Subjects were enrolled at the University of Texas Medical Branch in the Institute for Translational Sciences Clinical Research Center (ITS-CRC).

Participant flow — Overall Study
MilestonePlaceboMonthly Cycled TestosteroneContinuous Testosterone
Started899
Completed888
Not completed011
Withdrew: Protocol violation010
Withdrew: Withdrawal by subject001

Outcome measures

PrimaryChanges in Basal Muscle Protein Synthesis and Breakdown as Measured by Stable Isotope Metabolic Studies at Baseline and at Five Months

The fractional synthetic rate (FSR) of mixed muscle is calculated by directly measuring the incorporation of L-\[ring-13C6\]-phenylalanine into protein (%/hr),, using the precursor-product model: FSR = \[(EP2 - EP1)/(EM•t)\]•60•100, where EP1 and EP2 are the enrichments of bound L-\[ring-13C6\]-phenylalanine in the first and second muscle biopsies, t is the time interval (min) between biopsies, and EM is the mean L-\[ring-13C6\]-phenylalanine enrichment in the muscle intracellular pool.

Time frame:
5 Months
Reported as:
Mean · Percent per hour (%/hr)
Changes in Basal Muscle Protein Synthesis and Breakdown as Measured by Stable Isotope Metabolic Studies at Baseline and at Five Months
Percent per hour (%/hr)PlaceboMonthly Cycled TestosteroneContinuous Testosterone
Baseline0.05 ± 0.010.06 ± 0.010.06 ± 0.01
Five Months0.066 ± 0.0200.094 ± 0.0140.101 ± 0.043
PrimaryChanges in Muscle Strength as Measured by Maximal Voluntary Contraction Tests (Arm Curl) at Baseline, One Month, Two Months, Three Months, Four Months, and at Five Months

Maximum weight (pounds) lifted using Cybex weight machine in a single effort(1-RM) for upper extremities (biceps and triceps) and lower extremities quadriceps and hamstrings).

Time frame:
5 months
Reported as:
Mean · pounds
Changes in Muscle Strength as Measured by Maximal Voluntary Contraction Tests (Arm Curl) at Baseline, One Month, Two Months, Three Months, Four Months, and at Five Months
poundsPlaceboMonthly Cycled TestosteroneContinuous Testosterone
Arm Curl Baseline39 ± 1239 ± 1032 ± 9
Arm Extension Baseline40 ± 941 ± 1438 ± 9
Leg Curl Baseline46 ± 644 ± 740 ± 9
Leg Extension Baseline70 ± 2173 ± 1566 ± 16
Arm Curl Month 139 ± 1041 ± 1034 ± 8
Arm Curl Month 238 ± 940 ± 1039 ± 9
Arm Curl Month 339 ± 943 ± 1137 ± 13
Arm Curl Month 438 ± 1043 ± 1341 ± 12
Arm Curl Month 540 ± 1145 ± 1338 ± 11
Arm Extension Month 140 ± 741 ± 1037 ± 4
Arm Extension Month 241 ± 842 ± 944 ± 10
Arm Extension Month 342 ± 843 ± 744 ± 14
Arm Extension Month 442 ± 844 ± 844 ± 12
Arm Extension Month 542 ± 845 ± 845 ± 10
Leg Curl Month 148 ± 746 ± 941 ± 8
Leg Curl Month 251 ± 1147 ± 948 ± 11
Leg Curl Month 348 ± 743 ± 2048 ± 14
Leg Curl Month 448 ± 750 ± 1050 ± 12
Leg Curl Month 548 ± 1050 ± 1151 ± 12
Leg Extension Month 170 ± 1373 ± 1067 ± 15
Leg Extension Month 269 ± 1477 ± 1678 ± 12
Leg Extension Month 374 ± 1380 ± 1476 ± 21
Leg Extensuion Month 472 ± 1479 ± 1682 ± 14
Leg Extension Month 572 ± 1485 ± 1983 ± 17
PrimaryChanges in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA)

Lean body mass is expressed in grams as calculated by Hologic DEXA.

Time frame:
5 months
Reported as:
Mean · grams
Changes in Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA)
gramsPlaceboMonthly Cycled TestosteroneContinuous Testosterone
Lean Body Mass Baseline62344 ± 1036857101 ± 6671.557746 ± 6485.1
Lean Body Mass Month 162994.7 ± 10308.859155.4 ± 6890.960469.3 ± 6555.92
Lean Body Mass Month 262038.7 ± 10556.556787.8 ± 6444.1662680.1 ± 4034.41
Lean Body Mass Month 362256.5 ± 9881.6559186 ± 6267.6361167.3 ± 7530.43
Lean Body Mass Month 462755.4 ± 10756.259838.6 ± 7010.7361436.6 ± 6997.17
Lean Body Month 561250.6 ± 11283.358846.9 ± 6995.4860871.4 ± 6840.45
SecondaryChanges in Bone Mineral Density as Measured by Dual Energy X-ray Absorptiometry (DEXA)

Bone mineral density measure by measured by dual energy x-ray absorptiometry (DEXA)measured at baseline and a five months

Time frame:
5 months
Reported as:
Mean · gm/cm^2
Changes in Bone Mineral Density as Measured by Dual Energy X-ray Absorptiometry (DEXA)
gm/cm^2PlaceboMonthly Cycled TestosteroneContinuous Testosterone
Total Baseline1.12 ± 0.041.07 ± 0.051.12 ± 0.05
Total Five Months1.08 ± 0.071.05 ± 0.051.14 ± 0.03
Lumbar Spine Baseline1.06 ± 0.071.00 ± 0.051.16 ± 0.04
Lumbar Spine Five Months1.07 ± 0.071.00 ± 0.051.19 ± 0.06
Pelvis baseline1.46 ± 0.161.15 ± 0.041.27 ± 0.04
Pelvis Five Months1.28 ± 0.141.14 ± 0.041.28 ± 0.06
Forearm Baseline0.59 ± 0.020.59 ± 0.020.61 ± 0.02
Forearm Five Months0.61 ± 0.020.59 ± 0.030.62 ± 0.03
SecondaryChanges in Serum Markers of Bone Turnover.

Measures of bone turnover markers in serum samples at baseline and at five months.The bone turnover markers analyzed include: Markers associated with bone breakdown NTX (N-telopeptide) TRAP5b (tartrate-resistant acid phosphatase isoform 5b) Markers associated with bone formation Osteocalcin BAP (bone specific alkaline phosphatase) Regulators of bone formation iPTH (intact parathyroid hormone) increases in response to bone loss Calcitonin inhibits bone formation in response to elevated levels of serum calcium

Time frame:
5 months
Reported as:
Mean · nM BCE (Bone Collagen Equivalents)
Changes in Serum Markers of Bone Turnover.
nM BCE (Bone Collagen Equivalents)PlaceboMonthly Cycled TestosteroneContinuous Testosterone
NTX Baseline12 ± 1.314 ± 1.415 ± 1.9
NTX Five Months13 ± 1.111 ± 0.711 ± 1.5
TRAP5b Baseline2 ± 0.62 ± 0.62 ± 0.4
TRAP5b Five Months2 ± 0.62 ± 0.61 ± 0.3
Osteocalcin Baseline8 ± 0.28 ± 0.69 ± 0.7
Osteocalcin Five Months8 ± 0.58 ± 0.57 ± 0.8
BAP Baseline22 ± 1.520 ± 2.317 ± 1.5
BAP Five Months21 ± 1.319 ± 1.915 ± 1.7
iPTH Baseline40 ± .337 ± 653 ± 10
iPTH Five Months45 ± 728 ± 360 ± 15
Calcitonin Baseline3 ± 0.44 ± 0.64 ± 1.3
Calcitonin Five months3 ± 0.44 ± 0.53 ± 0.3
Secondary9473Changes in Serum Inflammatory Biomarkers and Muscle Inflammatory Cytokines

Serum inflammatory biomarkers (Interleukin B-1, 2,5,6,7,8,10,12 13, Interferon gamma, GM-CSF, and Tumor Necrosis Factor alpha)as measured by immunoassay at baseline and at five months

Time frame:
5 months
Reported as:
Mean · pg/mL
9473Changes in Serum Inflammatory Biomarkers and Muscle Inflammatory Cytokines
pg/mLPlaceboMonthly Cycled TestosteroneContinuous Testosterone
IL-B1 Baseline0.14 ± 0.10.475 ± 0.767671.44143 ± 2.04769
IL-B1 Five Months0.20833 ± 0.222213.19 ± 3.246432.538 ± 3.33404
IL-2 Baseline1.32 ± 1.186553.19 ± 3.246432.538 ± 3.33404
IL-2 Five Months2.84 ± 1.990081.45333 ± 0.940763.862 ± 5.90798
IL-5 Baseline0.6 ± 0.715290.79 ± 0.767831.41875 ± 1.92013
IL-5 Five Months0.705 ± 1.328980.32286 ± 0.300651.94125 ± 3.46852
IL-6 Baseline5.68375 ± 6.782934.90857 ± 6.4327710.4025 ± 20.5897
IL-6 Five months5.05 ± 6.06436.487 ± 178.67313.89 ± 28.8691
IL-7 Baseline8.78 ± 10.407611.9688 ± 16.21355.19875 ± 2.84198
IL-7 Five Months7.68 ± 10.89823.1888 ± 52.370516.2763 ± 19.6011
IL-8 Baseline4.5575 ± 2.670116.66375 ± 4.509338.45625 ± 11.836
IL-8 Five months4.3225 ± 2.08724.06286 ± 1.7679511.8025 ± 20.6936
IL-10 Baseline22.6363 ± 41.888311.2588 ± 8.19838109.446 ± 240.088
IL-10 Five Months25.4525 ± 41.41358.34143 ± 3.65748135.64 ± 265.7
IL-12 Baseline7.075 ± 12.38054.242 ± 4.0705235.3583 ± 56.0444
IL-12 Five Months10.902 ± 17.41432.66 ± 3.799358.4217 ± 86.8424
IL-13 baseline37.045 ± 51.922923.33 ± 48.702960.2125 ± 102.473
IL-13 Five Months43.465 ± 61.058712.72 ± 17.268773.674 ± 148.613
IFN gamma Baseline10.115 ± 15.72194.58 ± 7.6394323.425 ± 28.8768
IFN gamma Five Months36.05 ± 68.73091.758 ± 1.9848636.822 ± 69.571
GM-CSF Baseline1.52429 ± 2.462862.4 ± 2.586397.94875 ± 16.6389
GM-CSF Five Months2.27857 ± 3.191991.312 ± 0.8864914.965 ± 37.1713
TNF alpha Baseline9.0175 ± 4.6079310.0863 ± 4.5105813.215 ± 10.1743
TNF alpha Five Months8.14 ± 3.957788.1529 ± 3.7096515.4138 ± 13.0438

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—0/8 (0%)1/8 (12.5%)
Monthly Cycled Testosterone—0/8 (0%)0/8 (0%)
Continuous Testosterone—0/8 (0%)1/8 (12.5%)
Most frequent other events
Most frequent other events
EventPlaceboMonthly Cycled TestosteroneContinuous Testosterone
Saphenous vein clotVascular disorders1/80/81/8
vertigoNervous system disorders1/80/81/8

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)PlaceboMonthly Cycled TestosteroneContinuous TestosteroneTotal
<=18 years0000
Between 18 and 65 years53210
>=65 years36716
Age Continuous
Age Continuous(years)PlaceboMonthly Cycled TestosteroneContinuous TestosteroneTotal
Mean65.4 ± 3.2271.6 ± 7.7873.3 ± 7.5470.1 ± 6.18
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboMonthly Cycled TestosteroneContinuous TestosteroneTotal
Female0000
Male89926
Region of Enrollment
Region of Enrollment(participants)PlaceboMonthly Cycled TestosteroneContinuous TestosteroneTotal
United States89926
08

Study locations

1 site
  • University of Texas Medical Branch
    Galveston, Texas 77555, United States
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Jan 2006, a primary completion of Dec 2008 and a completion of Dec 2008. It does not say whether these dates are actual or estimated.

Results were first posted in Aug 2012, 3 years 8 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 10, 2009
First posted
Aug 12, 2009
Start
Jan 2006
Primary completionActual
Dec 2008
CompletionActual
Dec 2008
Results first posted
Aug 21, 2012
Last update
Sep 10, 2012
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 10, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00957528
Lead sponsor
The University of Texas Medical Branch, Galveston
Responsible party
Sponsor
First posted
Aug 12, 2009
Start date
Jan 2006
Primary completion
Dec 2008
Completion
Dec 2008
Results posted
Aug 21, 2012
Last update
Sep 10, 2012

Study contacts

Randall J Urban, M.D.
principal investigator · University of Texas

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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