Droxidopa / Pyridostigmine in Orthostatic Hypotension

Mayo Clinic

Status and phase: Invitation-only; Phase 2

Conditions: Orthostatic Hypotension

Treatments: Drug: Droxidopa; Other: Placebo; Drug: Pyridostigmine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01370512

P01NS044233 (U.S. NIH Grant/Contract)

10-008810

Details and patient eligibility

About

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

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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with midodrine, alpha and beta adrenergic antagonists, or other medications that affect autonomic function will be withdrawn 48 hours prior to autonomic evaluations.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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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30 participants in 4 patient groups

Placebo, Then Pyridostigmine

Active Comparator group

Description:

participants first receive placebo by mouth 3 times a day, for treatment day 1. Then participants receive pyridostigmine by mouth 3 times a day for treatment day 2.

Treatment:

Drug: Pyridostigmine

Other: Placebo

Pyridostigmine, Then Placebo

Active Comparator group

Description:

participants first receive pyridostigmine by mouth 3 times a day, for treatment day 1. Then participants receive placebo by mouth 3 times a day for treatment day 2.

Treatment:

Drug: Pyridostigmine

Other: Placebo

Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine

Experimental group

Description:

participants first receive placebo by mouth 3 times a day, for treatment day 3. Then participants receive Droxidopa by mouth 3 times a day for treatment day 4.

Treatment:

Drug: Pyridostigmine

Other: Placebo

Drug: Droxidopa

Droxidopa and Pyridostigmine, Then Droxidopa and Placebo

Experimental group

Description:

participants first receive Droxidopa by mouth 3 times a day, for treatment day 3. Then participants receive Placebo by mouth 3 times a day for treatment day 4.

Treatment:

Drug: Pyridostigmine

Other: Placebo

Drug: Droxidopa