Droxidopa / Pyridostigmine in Orthostatic Hypotension

Treatment Trial of Droxidopa and Pyridostigmine to Improve Orthostatic Hypotension Without Aggravating Supine Hypertension

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

Study Overview

• Status: Suspended
• Conditions: Orthostatic Hypotension
• Intervention / Treatment: Drug: Pyridostigmine; Other: Placebo; Drug: Droxidopa

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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with midodrine, alpha and beta adrenergic antagonists, or other medications that affect autonomic function will be withdrawn 48 hours prior to autonomic evaluations.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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Placebo, Then Pyridostigmine; 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.	Drug: Pyridostigmine; 60 mg tablets by mouth three times a day; Other: Placebo; Looks exactly like the study drug but contains no active ingredients
Active Comparator: Pyridostigmine, Then Placebo; 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.	Drug: Pyridostigmine; 60 mg tablets by mouth three times a day; Other: Placebo; Looks exactly like the study drug but contains no active ingredients
Experimental: Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine; 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.	Drug: Pyridostigmine; 60 mg tablets by mouth three times a day; Other: Placebo; Looks exactly like the study drug but contains no active ingredients; Drug: Droxidopa; 100 mg tablets by mouth three times a day
Experimental: Droxidopa and Pyridostigmine, Then Droxidopa and Placebo; 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.	Drug: Pyridostigmine; 60 mg tablets by mouth three times a day; Other: Placebo; Looks exactly like the study drug but contains no active ingredients; Drug: Droxidopa; 100 mg tablets by mouth three times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in orthostatic diastolic blood pressure	diastolic blood pressure measured upon standing reported in mm/Hg	1 hour after medication administration, 2 hours after medication administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in orthostatic systolic blood pressure	systolic blood pressure measured upon standing reported in mm/Hg	1 hour after medication administration, 2 hours after medication administration
Change in absolute supine diastolic blood pressure	diastolic blood pressure measured while lying flat reported in mm/Hg	1 hour after medication administration, 2 hours after medication administration
Change in absolute supine systolic blood pressure	systolic blood pressure measured while lying flat reported in mm/Hg	1 hour after medication administration, 2 hours after medication administration
Change in supine norepinephrine levels	measure of serum norepinephrine levels while lying flat reported in pg/mL	1 hour after medication administration, 2 hours after medication administration
Change in orthostatic symptoms	measured during tilt study, the patient will be asked to score orthostatic symptoms on a symptom scale ranging from "0" = no symptoms to "10" = near syncope	1 hour after medication administration, 2 hours after medication administration

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Phillip A Low, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: June 8, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimated): June 10, 2011

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Nervous System Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Hypotension; Hypotension, Orthostatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Cholinesterase Inhibitors; Droxidopa; Pyridostigmine Bromide
• Other Study ID Numbers: 10-008810; P01NS044233 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No