Hypertension
Conditions
Brief summary
This study will evaluate methodologies for measuring pedal edema associated with calcium channel blockers in middle-aged and elderly subjects and patients with hypertension.
Interventions
Two 5 mg tablets amlodipine daily for 6 weeks.
DRUGComparator: Placebo
Two 5 mg tablets placebo to amlodipine daily for 6 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Patient does not have hypertension or has Stage I or II hypertension and is taking \< 3 anti-hypertension medications * Patient is willing to discontinue all anti-hypertensive medications during study * Patient is willing to refrain from drinking alcohol for 24 hours prior to each study visit and is willing to limit intake at other times during the study to 2 drinks per day * Patient agrees to avoid caffeine for 24 hours prior to each study visit. At other times during study, daily caffeine intake should not exceed 4 cups of coffee (or equivalent) * Patient will avoid strenuous physical activity during study * Patient is a nonsmoker or has not smoked for the last 3 months
Exclusion criteria
* Patient has metal implants in the leg or artificial limbs * Patient has had a lower limb amputation, malformation, alterations in leg muscles, or a history of musculoskeletal disease * Patient has used oral contraceptive pills or hormone replacement therapy within 3 months of screening * Patient has a history of stroke or seizures * Patient has a history of cancer, except that which was treated at least 10 years prior to screening and shows no evidence of recurrence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Segmental Bioimpedance Measurements at 10 Kilohertz (KHz) at Week 2 | Baseline and 2 weeks | Segmental biomimpedance was measured using a multifrequency analyzer (ImpediMed SFB7). The device was used to measure impedance (measured in Ohms) of a small current traveling between leads placed at the ankle and knee. Least Squares Mean Difference from Baseline in impedance is the primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Foot Volume by Water Displacement (Weight of Water Displaced) at Week 2 | Baseline and 2 weeks | Least Squares Mean Difference from Baseline |
Participant flow
Recruitment details
Participants were recruited across 3 Phase I clinical research units in the US. Participants participated from July 2008 to March 2009.
Pre-assignment details
Participants taking anti-hypertensive medications at screening were required to washout of this therapy before randomization and remain off the therapy during the study. Participants were eligible if systolic blood pressure (BP) was ≥120 to \<180 mm Hg and diastolic BP was ≥80 to \<110 mm Hg at screening (or after 2-4 weeks of washout, if applicable)
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine 10 Milligrams Participants who were randomized to treatment with amlodipine 10 mg once daily for 6 weeks | 24 |
| Placebo Participants who were randomized to treatment with placebo once daily for 6 weeks | 23 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Amlodipine 10 Milligrams | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 5.6 | 59.6 years STANDARD_DEVIATION 6.2 | 59.0 years STANDARD_DEVIATION 5.9 |
| Body Mass Index | 28.2 kg/m^2 STANDARD_DEVIATION 2.9 | 29.0 kg/m^2 STANDARD_DEVIATION 2.7 | 28.6 kg/m^2 STANDARD_DEVIATION 2.8 |
| Sex: Female, Male Female | 13 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 11 Participants | 12 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 24 | 16 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 |
Outcome results
Primary
Change From Baseline in Segmental Bioimpedance Measurements at 10 Kilohertz (KHz) at Week 2
Segmental biomimpedance was measured using a multifrequency analyzer (ImpediMed SFB7). The device was used to measure impedance (measured in Ohms) of a small current traveling between leads placed at the ankle and knee. Least Squares Mean Difference from Baseline in impedance is the primary endpoint.
Time frame: Baseline and 2 weeks
Population: All patients treated with segmental bioimpedance measurements at baseline and 2 weeks - one patient in the placebo group was not included (dropped out of study due to viral infection prior to Week 2).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine 10 Milligrams | Change From Baseline in Segmental Bioimpedance Measurements at 10 Kilohertz (KHz) at Week 2 | -7.9 Ohms | Standard Deviation 20.7 |
| Placebo | Change From Baseline in Segmental Bioimpedance Measurements at 10 Kilohertz (KHz) at Week 2 | 3.8 Ohms | Standard Deviation 17 |
p-value: 0.00190% CI: [-18.1, -5.4]ANCOVA
Secondary
Change From Baseline in Foot Volume by Water Displacement (Weight of Water Displaced) at Week 2
Least Squares Mean Difference from Baseline
Time frame: Baseline and 2 weeks
Population: All patients treated with water displacement measurements at baseline and 2 weeks - one patient in the placebo group was not included (dropped out of study due to viral infection prior to Week 2) - two patients in the amlodipine group were excluded due to technical/procedural errors.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine 10 Milligrams | Change From Baseline in Foot Volume by Water Displacement (Weight of Water Displaced) at Week 2 | 44.8 Grams | Standard Deviation 64.8 |
| Placebo | Change From Baseline in Foot Volume by Water Displacement (Weight of Water Displaced) at Week 2 | 5.8 Grams | Standard Deviation 53.2 |
p-value: 0.00195% CI: [17.9, 60.1]ANCOVA