Droxidopa / Pyridostigmine in Orthostatic Hypotension

NCT01370512 | Enrolling By Invitation Phase 2 FDA Drug

• 2 other identifiers: 10-008810P01NS044233
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Orthostatic Hypotension

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change in orthostatic systolic blood pressure

  1 hour after medication administration, 2 hours after medication administration

• Change in absolute supine diastolic blood pressure

  1 hour after medication administration, 2 hours after medication administration

• Change in absolute supine systolic blood pressure

  1 hour after medication administration, 2 hours after medication administration

• Change in supine norepinephrine levels

  1 hour after medication administration, 2 hours after medication administration

• Change in orthostatic symptoms

  1 hour after medication administration, 2 hours after medication administration

Study Arms (4)

Placebo, Then Pyridostigmine

ACTIVE COMPARATOR

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; Other: Placebo

Pyridostigmine, Then Placebo

ACTIVE COMPARATOR

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; Other: Placebo

Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine

EXPERIMENTAL

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: Droxidopa; Drug: Pyridostigmine; Other: Placebo

Droxidopa and Pyridostigmine, Then Droxidopa and Placebo

EXPERIMENTAL

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: Droxidopa; Drug: Pyridostigmine; Other: Placebo

Interventions

Droxidopa DRUG

100 mg tablets by mouth three times a day

Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine; Droxidopa and Pyridostigmine, Then Droxidopa and Placebo

Pyridostigmine DRUG

60 mg tablets by mouth three times a day

Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine; Droxidopa and Pyridostigmine, Then Droxidopa and Placebo; Placebo, Then Pyridostigmine; Pyridostigmine, Then Placebo

Placebo OTHER

Looks exactly like the study drug but contains no active ingredients

Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine; Droxidopa and Pyridostigmine, Then Droxidopa and Placebo; Placebo, Then Pyridostigmine; Pyridostigmine, Then Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Pregnant or lactating females.
• 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.
• Orthopedic problems or cardiopulmonary disease, sufficient to compromise mobility and activity of daily living.
• Any known concurrent infection or severe liver or kidney disease.
• 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.
• 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.
• 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.
• Dementia (DSM-IV criteria - Amer. Psych. Assoc., 1994). The score on the Mini-Mental State Examination must be \>24.
• 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).
• History of electroconvulsive therapy.
• History of brain surgery for Parkinson's disease.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Hypotension, Orthostatic

Interventions

Droxidopa; Pyridostigmine Bromide

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Wolfgang Singer, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Placebo-controlled, double-blind, randomized four-way crossover

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 10, 2011
• Study Start: November 1, 2011
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)