Clinical trial NCT01370512: Droxidopa / Pyridostigmine in Orthostatic Hypotension
Official title: Treatment Trial of Droxidopa and Pyridostigmine to Improve Orthostatic Hypotension Without Aggravating Supine Hypertension
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Orthostatic Hypotension
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2011-06-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Placebo-controlled, double-blind, randomized four-way crossover
Primary purpose: TREATMENT

Brief summary: This study is being done to study the combination of pyridostigmine and low-dose Droxidopa for the treatment of orthostatic hypotension.


Eligibility criteria: Inclusion Criteria

1. The presence of OH (fall in systolic BP \>=30 mm Hg) is required for this study.
2. Autonomic testing and clinical evaluation demonstrates OH to be of neurogenic etiology.

Exclusion Criteria:

1. Pregnant or lactating females.
2. Chronic illnesses or the presence of other conditions that potentially involve the CNS or affect autonomic testing. These include congestive heart failure, recent (\<6 months) myocardial infarct, severe anemia, diabetes mellitus, alcoholism, malignant neoplasms, amyloidosis, hypothyroidism, sympathectomy, cerebrovascular accidents, and neurotoxins or neuroactive drug exposure.
3. Orthopedic problems or cardiopulmonary disease, sufficient to compromise mobility and activity of daily living.
4. Any known concurrent infection or severe liver or kidney disease.
5. Medications that could affect autonomic function are suspended prior to autonomic testing. Therapy with midodrine, alpha and beta adrenergic antagonists, or other medications that affect autonomic function will be withdrawn 48 hours prior to autonomic evaluations. Fludrocortisone doses up to 0.2 mg per day will be permitted. Stable doses of antidepressants (tricyclics, SSRIs, SNRIs) will also be permitted. The 48h medication withdrawal is reviewed on a case by case basis - if felt unsafe by the investigators, the withdrawal period may be shortened. This will be documented in the study documents.
6. Occasional use of a neuroleptic as an anti-emetic in the past is allowed, but none can have been used within 3 weeks prior to this study.
7. Use of methylphenidate, cinnarizine, reserpine, amphetamine, atypical antipsychotics such as risperidone, olanzapine, and quetiapine or a MAO-A inhibitor within 3 weeks prior to this study.
8. Dementia (DSM-IV criteria - Amer. Psych. Assoc., 1994). The score on the Mini-Mental State Examination must be \>24.
9. History of stroke (diagnosed on clinical grounds as an acute deterioration of neurological function typical of a stroke; confirmatory CT or MRI evidence of stroke will be useful but not necessary).
10. History of electroconvulsive therapy.
11. History of brain surgery for Parkinson's disease.

Primary outcomes:
measure: Change in orthostatic diastolic blood pressure
timeFrame: 1 hour after medication administration, 2 hours after medication administration
Secondary outcomes:
measure: Change in orthostatic systolic blood pressure
timeFrame: 1 hour after medication administration, 2 hours after medication administration
measure: Change in absolute supine diastolic blood pressure
timeFrame: 1 hour after medication administration, 2 hours after medication administration
measure: Change in absolute supine systolic blood pressure
timeFrame: 1 hour after medication administration, 2 hours after medication administration
measure: Change in supine norepinephrine levels
timeFrame: 1 hour after medication administration, 2 hours after medication administration
measure: Change in orthostatic symptoms
timeFrame: 1 hour after medication administration, 2 hours after medication administration
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Phillip A Low, M.D.
role: PRINCIPAL_INVESTIGATOR
References: