Kidney Diseases, Kidney Failure
Conditions
Brief summary
Muscle wasting is common in advanced chronic kidney disease (CKD) and adversely affects morbidity and mortality. In 2/3 of males with advanced CKD serum testosterone (TT) levels are reduced, and likely contributes to the wasting. As TT in relatively safe physiologic replacement doses, increases muscle mass in otherwise normal TT deficient subjects, we hypothesize that physiologic TT replacement will be effective in preventing and treating the loss of muscle mass and function in CKD patients, will improve quality of life and may reduce some cardiovascular disease (CVD) risk factors.
Detailed description
All subjects will undergo baseline testing that will consist of functional capacity tests, blood tests and muscle biopsies (described in detail below). Subjects will then receive testosterone gel which will be applied daily to the skin of the abdomen or thighs every morning at the same time for 16 weeks. Two days after the hormone treatment is started, the blood testosterone (TT) level will be measured 6 hours after administration. Our goal will be the attainment of serum total TT levels in the mid- to upper normal young adult range. If the serum TT is not at goal, the dose of gel will be increased or decreased repeat testing will be performed within one week. All subjects will be tested for serum TT levels every 4 weeks to assure that the serum total TT remains at goal level. Measurements will be repeated at 8 and 16 weeks.
Interventions
DRUGTestim, 1% testosterone gel
Subjects apply contents of gel packet (Testim, 1% testosterone gel) to skin daily.
Sponsors
Palo Alto Veterans Institute for Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria: CKD subjects; males with calculated GFR (MRDR equation) between 15 and 40 ml/min/1.73m2 and stable or slowly progressive renal failure (decline in function of \<1ml/min/month) including those patients requiring hemodialysis and serum testosterone levels of \<300 ng/ml and capable of safely performing required exercise testing and serum testosterone levels of \<300ng/ml and capable of safely performing required exercise testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thigh Cross Sectional Area | Baseline | DEXA-determined thigh cross-sectional area |
| Lean Body Mass | Baseline | DEXA-determined lean body mass |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kidney Disease-Specific Quality of Life | Baseline | Questionnaire - SF-36, which stands for the Short Form 36 Health Survey. It is a widely used standardized 36 item quality of life assessment. This particular measure focused on symptoms, and is scaled from zero to 100, with a higher score indicating better health functioning. |
| Fat Mass | Baseline | DEXA-determined total body fat mass |
| Muscle Atrophy Signaling Pathways | Baseline | These include muscle growth regulatory factors, IGF-1 and myostatin, their receptors and components of the ubiquitin-proteasome and calpain proteolytic pathways and inflammatory cytokines. |
| Inflammatory Markers | pre treatment and monthly until end of treatment | C-Reactive Protein (CRP). CRP is measured in mg/l and is a marker of inflammation. CRP generally ranges from \<1.0 to 5 mg/L. A normal value is less than 2.0 mg/L. |
| Quadriceps Strength | Baseline | Lower body strength (in lbs) using quadriceps leg extension. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chronic Kidney Disease Patients with chronic kidney disease between the ages of 55 and 75 years.
Testim (1% testosterone gel): Subjects apply contents of gel packet to skin daily. | 9 |
| Control Control participants with baseline data collection only (for baseline comparator). | 8 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not complete all assesments | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Chronic Kidney Disease | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Continuous | 60.2 years STANDARD_DEVIATION 11.1 | 61.3 years STANDARD_DEVIATION 8.9 | 60.7 years STANDARD_DEVIATION 9.9 |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 6 Participants | 7 Participants |
| Region of Enrollment United States | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 |
| other Total, other adverse events | 0 / 9 | 0 / 8 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 |
Outcome results
Primary
Lean Body Mass
DEXA-determined lean body mass
Time frame: Baseline
Population: Outcome measure data were collected from CKD participants only; CKD participants who completed the protocol are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronic Kidney Disease | Lean Body Mass | 48.2 Kg | Standard Deviation 9 |
Primary
Thigh Cross Sectional Area
DEXA-determined thigh cross-sectional area
Time frame: Baseline
Population: Outcome measure data were collected from CKD participants only; CKD participants who completed the protocol are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronic Kidney Disease | Thigh Cross Sectional Area | 58.2 centimeters squared | Standard Deviation 11 |
Secondary
Fat Mass
DEXA-determined total body fat mass
Time frame: Baseline
Population: Outcome measure data were collected from CKD participants only; CKD participants who completed the protocol are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronic Kidney Disease | Fat Mass | 21.2 Kg | Standard Deviation 7 |
Secondary
Inflammatory Markers
C-Reactive Protein (CRP). CRP is measured in mg/l and is a marker of inflammation. CRP generally ranges from \<1.0 to 5 mg/L. A normal value is less than 2.0 mg/L.
Time frame: pre treatment and monthly until end of treatment
Secondary
Kidney Disease-Specific Quality of Life
Questionnaire - SF-36, which stands for the Short Form 36 Health Survey. It is a widely used standardized 36 item quality of life assessment. This particular measure focused on symptoms, and is scaled from zero to 100, with a higher score indicating better health functioning.
Time frame: Baseline
Population: Outcome measure data were collected from CKD participants only; CKD participants who completed the protocol are included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chronic Kidney Disease | Kidney Disease-Specific Quality of Life | 42.1 units on a scale | Standard Deviation 8.1 |
Secondary
Muscle Atrophy Signaling Pathways
These include muscle growth regulatory factors, IGF-1 and myostatin, their receptors and components of the ubiquitin-proteasome and calpain proteolytic pathways and inflammatory cytokines.
Time frame: Baseline
Secondary
Quadriceps Strength
Lower body strength (in lbs) using quadriceps leg extension.
Time frame: Baseline