Heart Failure
Conditions
Keywords
Leg Weakness, Skeletal Myopathy, Sympathetic Nerve Activity
Brief summary
People with heart failure often have weakness in their leg muscles. This study will determine whether the leg weakness is due to very high adrenaline levels and whether the medication clonidine can improve leg weakness.
Detailed description
Heart failure is a common condition, affecting approximately 5 million people in the United States. People with heart failure are encouraged to exercise and lose weight. However, many people with heart failure develop weakness in their leg muscles, which can make exercise difficult. Increased sympathetic nerve activity, which involves the nerves that carry adrenaline, also occurs in people with heart failure. It is possible that the increased sympathetic nerve activity may actually cause the leg muscle weakness. Clonidine, a medication used to treat high blood pressure, has been found to decrease sympathetic nerve activity. This study will further examine the connection between leg weakness and sympathetic nerve activity. It will also evaluate the effectiveness of clonidine at decreasing leg weakness in people with heart failure. Results from this study may explain why some people with heart failure are unable to exercise and may help to identify ways in which leg strength can be increased. This study will enroll people with heart failure. Participants will be randomly assigned to wear either a clonidine patch or a placebo patch for 3 months. Participants will wear the patch on their upper arm, and they will replace the patch each week. At study visits at baseline and Month 3, participants will undergo the following procedures: * Sympathetic nerve activity recording, which will record nerve activity in the lower leg, using small electrodes inserted through the skin * Muscle biopsy, in which a small piece of muscle tissue will be obtained from participants' legs * Heart rate and blood pressure measurements * Arterial baroreceptor measurements, in which the nerves in the body that respond to changes in blood pressure will be examined while participants receive different medications to increase and decrease their blood pressure * Echocardiography to obtain images of the heart * Magnetic resonance scan of the leg * Passive exercise procedure, in which study researchers will conduct an arm exercise with participants There will be no follow-up visits.
Interventions
DRUGClonidine Patch
A clonidine patch (0.1 mg/week) to be worn for a period of 3 months.
A matching placebo patch to be worn for a period of 3 months.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Heart failure
Exclusion criteria
* Currently on Coumadin therapy * Experienced a heart attack in the 3 months before study entry * Medically unable to receive clonidine * Advanced kidney or liver disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Citrate Synthase Activity as an Estimate of Mitochondrial Activity | Baseline, 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Proportion of Type 1 Fibers | Baseline, 3 months | Fibers were typed as I or II according to presence of myosin heavy chain. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Muscle Sympathetic Nerve Activity | Baseline, 3 months | Muscle sympathetic nerve activity was measured as bursts sympathetic nerve activity per minute. |
Countries
United States
Participant flow
Recruitment details
All heart failure patients were recruited from the Ahmanson-University of California, Los Angeles (UCLA) Cardiomyopathy Center between 2008-2011.
Pre-assignment details
Of 44 heart failure patients interested, 25 were ineligible (medication changes (6), too well with either left ventricular ejection fraction(LVEF) \>35% (3) or New York Heart Association (NYHA) Class I (2), transportation issues (4), morbidly obese (3), enrolled in exercise program (2), other (5)), and of the remaining 19 patients, 8 declined.
Participants by arm
| Arm | Count |
|---|---|
| Clonidine Patch Participants were assigned to wear a clonidine patch (0.1 mg/weekly) for a treatment period of 3 months. | 5 |
| Placebo Patch Participants were assigned to wear a matching placebo patch (0.1 mg/weekly) for a treatment period of 3 months. | 6 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Patient underwent heart transplant. | 0 | 1 |
Baseline characteristics
| Characteristic | Clonidine Patch | Placebo Patch | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 6 Participants | 11 Participants |
| Region of Enrollment United States | 5 participants | 6 participants | 11 participants |
| Sex/Gender, Customized Female | NA participants | NA participants | 4 participants |
| Sex/Gender, Customized Male | NA participants | NA participants | 7 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 0 / 5 | 0 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 |
Outcome results
Primary
Change in Citrate Synthase Activity as an Estimate of Mitochondrial Activity
Time frame: Baseline, 3 months
Population: One patient randomized to placebo underwent urgent orthotopic heart transplantation before second measure could be obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clonidine Patch | Change in Citrate Synthase Activity as an Estimate of Mitochondrial Activity | -0.3 micromole/min/wet weight | Standard Error 0.09 |
| Placebo | Change in Citrate Synthase Activity as an Estimate of Mitochondrial Activity | 0.07 micromole/min/wet weight | Standard Error 0.07 |
Secondary
Change in Proportion of Type 1 Fibers
Fibers were typed as I or II according to presence of myosin heavy chain.
Time frame: Baseline, 3 months
Population: One patient randomized to placebo underwent urgent orthotopic heart transplantation before second measure could be obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clonidine Patch | Change in Proportion of Type 1 Fibers | -4.6 percentage of fibers | Standard Error 3.8 |
| Placebo | Change in Proportion of Type 1 Fibers | -5.6 percentage of fibers | Standard Error 1.9 |
Other Pre-specified
Change in Muscle Sympathetic Nerve Activity
Muscle sympathetic nerve activity was measured as bursts sympathetic nerve activity per minute.
Time frame: Baseline, 3 months
Population: One patient randomized to placebo underwent urgent orthotopic heart transplantation before second measure could be obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clonidine Patch | Change in Muscle Sympathetic Nerve Activity | -4.3 bursts/min | Standard Error 2.4 |
| Placebo | Change in Muscle Sympathetic Nerve Activity | 4.4 bursts/min | Standard Error 8.8 |