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Droxidopa / Pyridostigmine in Orthostatic Hypotension

Primary Purpose

Orthostatic Hypotension

Status

Suspended

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Droxidopa

Pyridostigmine

Placebo

About this trial

This is an interventional treatment trial for Orthostatic Hypotension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

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.

Exclusion Criteria:

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with midodrine, alpha and beta adrenergic antagonists, or other medications that affect autonomic function will be withdrawn 48 hours prior to autonomic evaluations.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

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Placebo, Then Pyridostigmine

Pyridostigmine, Then Placebo

Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine

Droxidopa and Pyridostigmine, Then Droxidopa and Placebo

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Change in orthostatic diastolic blood pressure

diastolic blood pressure measured upon standing reported in mm/Hg

Secondary Outcome Measures

Change in orthostatic systolic blood pressure

systolic blood pressure measured upon standing reported in mm/Hg

Change in absolute supine diastolic blood pressure

diastolic blood pressure measured while lying flat reported in mm/Hg

Change in absolute supine systolic blood pressure

systolic blood pressure measured while lying flat reported in mm/Hg

Change in supine norepinephrine levels

measure of serum norepinephrine levels while lying flat reported in pg/mL

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

Full Information

NCT ID

NCT01370512

First Posted

June 8, 2011

Last Updated

June 1, 2023

Sponsor

Mayo Clinic

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

1. Study Identification

Unique Protocol Identification Number

NCT01370512

Brief Title

Droxidopa / Pyridostigmine in Orthostatic Hypotension

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Suspended

Why Stopped

Plan to increase enrollment due to preliminary data having lower statistical power than anticipated.

Study Start Date

November 2011 (undefined)

Primary Completion Date

May 2024 (Anticipated)

Study Completion Date

May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Mayo Clinic

Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Orthostatic Hypotension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

Placebo-controlled, double-blind, randomized four-way crossover

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo, Then Pyridostigmine

Arm Type

Active Comparator

Arm 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.

Arm Title

Pyridostigmine, Then Placebo

Arm Type

Active Comparator

Arm 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.

Arm Title

Drioxidopa and Placebo, Then Drioxidopa and Pyridostigmine

Arm Type

Experimental

Arm 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.

Arm Title

Droxidopa and Pyridostigmine, Then Droxidopa and Placebo

Arm Type

Experimental

Arm 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.

Intervention Type

Drug

Intervention Name(s)

Droxidopa

Intervention Description

100 mg tablets by mouth three times a day

Intervention Type

Drug

Intervention Name(s)

Pyridostigmine

Intervention Description

60 mg tablets by mouth three times a day

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Looks exactly like the study drug but contains no active ingredients

Primary Outcome Measure Information:

Title

Change in orthostatic diastolic blood pressure

Description

diastolic blood pressure measured upon standing reported in mm/Hg

Time Frame

1 hour after medication administration, 2 hours after medication administration

Secondary Outcome Measure Information:

Title

Change in orthostatic systolic blood pressure

Description

systolic blood pressure measured upon standing reported in mm/Hg

Time Frame

1 hour after medication administration, 2 hours after medication administration

Title

Change in absolute supine diastolic blood pressure

Description

diastolic blood pressure measured while lying flat reported in mm/Hg

Time Frame

1 hour after medication administration, 2 hours after medication administration

Title

Change in absolute supine systolic blood pressure

Description

systolic blood pressure measured while lying flat reported in mm/Hg

Time Frame

1 hour after medication administration, 2 hours after medication administration

Title

Change in supine norepinephrine levels

Description

measure of serum norepinephrine levels while lying flat reported in pg/mL

Time Frame

1 hour after medication administration, 2 hours after medication administration

Title

Change in orthostatic symptoms

Description

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

Time Frame

1 hour after medication administration, 2 hours after medication administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Phillip A Low, M.D.

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Links:

URL

https://www.mayo.edu/research/clinical-trials

Description

Mayo Clinic Clinical Trials

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Droxidopa / Pyridostigmine in Orthostatic Hypotension

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