Droxidopa / Pyridostigmine in Orthostatic Hypotension

• ClinicalTrials.gov Identifier: NCT01370512
• Recruitment Status: Completed
• First Posted: June 10, 2011
• Last Update Posted: June 23, 2022
• Sponsor: Mayo Clinic
• Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)
• Information provided by (Responsible Party): Phillip Low, Mayo Clinic

Study Description

Brief Summary:

The hypothesis is that pyridostigmine will improve the safety factor of ganglionic neural transmission, while Droxidopa will replete the postganglionic neuron of norepinephrine (NE). This combination should result in enhanced orthostatic release of NE. The investigators have already demonstrated that pyridostigmine does not raise supine blood pressure.

Condition or disease	Intervention/treatment	Phase
Orthostatic Hypotension	Drug: Droxidopa; Drug: Pyridostigmine; Other: Placebo; Other: Placebo 2	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Placebo-controlled, double-blind, randomized four-way crossover
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment Trial of Droxidopa and Pyridostigmine to Improve Orthostatic Hypotension Without Aggravating Supine Hypertension
• Study Start Date: November 2011
• Actual Primary Completion Date: January 19, 2021
• Actual Study Completion Date: January 19, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: droxidopa plus pyridostigmine; droxidopa 100mg by mouth three times a day plus pyridostigmine 60mg by mouth three times a day (one day)	Drug: Droxidopa; Droxidopa 100 mg three times a day; Drug: Pyridostigmine; Pyridostigmine 60 mg three times a day
Active Comparator: droxidopa; droxidopa 100mg by mouth three times a day plus placebo (for pyridostigmine) by mouth three times a day (one day)	Drug: Droxidopa; Droxidopa 100 mg three times a day; Other: Placebo 2; Placebo for pyridostigmine
Active Comparator: pyridostigmine; pyridostigmine 60mg by mouth three times a day plus placebo (for droxidopa) by mouth three times a day	Drug: Pyridostigmine; Pyridostigmine 60 mg three times a day; Other: Placebo; Placebo for droxidopa
Placebo Comparator: placebo; placebo (for pyridostigmine) by mouth three times a day plus placebo (for droxidopa) by mouth three times a day	Other: Placebo; Placebo for droxidopa; Other: Placebo 2; Placebo for pyridostigmine

Outcome Measures

Primary Outcome Measures :

1. Effect of treatment on the orthostatic decline in blood pressure [ Time Frame: 1h and 2h after medication ]
   Effect of treatment on the orthostatic decline in blood pressure at 1h and 2h after medication

Secondary Outcome Measures :

1. Effect of treatment on the absolute standing BP [ Time Frame: 1h and 2h after medication ]
   Effect of treatment on the absolute standing BP at 1h and 2h after medication
2. Effect of treatment on the absolute supine BP [ Time Frame: 1h and 2h after medication ]
   Effect of treatment on the absolute supine BP at 1h and 2h after medication
3. Effect of treatment on norepinephrine [ Time Frame: 1h and 2h after medication ]
   Effect of treatment on norepinephrine at 1h and 2h after medication
4. Effect of treatment on orthostatic symptoms [ Time Frame: 1h and 2h after medication ]
   Effect of treatment on orthostatic symptoms at 1h and 2h after medication

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

• Principal Investigator: Phillip A Low, M.D.; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Phillip Low, PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01370512
• Other Study ID Numbers: 10-008810; P01NS044233 ( U.S. NIH Grant/Contract )
• First Posted: June 10, 2011
• Last Update Posted: June 23, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypotension, Orthostatic; Hypotension; Vascular Diseases; Cardiovascular Diseases; Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Droxidopa; Pyridostigmine Bromide; Antiparkinson Agents; Anti-Dyskinesia Agents; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs