Trial Outcomes & Findings for Norepinephrine Transporter Blockade, Autonomic Failure (NETAF) (NCT NCT02784535)

Last Updated: 2023-09-13

Results Overview

The Orthostatic Hypotension Questionnaire (OHQ) , patient-reported assessment tool consisting of the OH Symptom Assessment (OHSA), OH Daily Activity Scale (OHDAS). The composite score is composed of 10 individual items: 6 items measure specific symptoms , the Orthostatic Hypotension Symptom Assessment (OHSA), and 4 items measure the impact of those symptoms on a patient daily activities, the Orthostatic Hypotension Daily Activity Scale (OHDAS). This scales helps to measure the impact of orthostatic symptoms on daily. Scale is between 0-10: where "0" is minimum Orthostatic symptoms and "10" is the maximum / worse possible severity of the symptoms. All items are scored 0 through 10 (higher scores = more impact) and summed into the respective total scores. The OHSA and OHDAS subscales averaged to compute the OHQ composite score.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

week 0 to week 4

Results posted on

2023-09-13

Participant Flow

25 subjects completed study at Vanderbilt University Medical Center, Nashville 15 subjects were enrolled at NYU School of Medicine,Langone Medical Center.NY

68 patients were screened, 20 subjects met exclusion criteria. 48 enrolled in the open-label, dose-optimization phase to identify "Atomoxetine responders" for eligibility to be randomized. 8 participants did not meet the response eligibility criteria, (Blood pressure too high (4), no response to drug (4) 40 patients randomized in the double-blind, placebo-controlled.

Participant milestones

Participant milestones
Measure	Atomoxetine Then Placebo Atomoxetine: norepinephrine transporter inhibitor Atomoxetine capsules 10 mg or 18 mg Three times a day Placebo: Placebo, three times a day	Placebo Then Atomoxetine Placebo: Placebo, Three times a day Atomoxetine: norepinephrine transporter inhibitor Atomoxetine capsules 10 mg or 18 mg Three times a day
Overall Study STARTED	20	20
Overall Study COMPLETED	19	18
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Atomoxetine Then Placebo Atomoxetine: norepinephrine transporter inhibitor Atomoxetine capsules 10 mg or 18 mg Three times a day Placebo: Placebo, three times a day	Placebo Then Atomoxetine Placebo: Placebo, Three times a day Atomoxetine: norepinephrine transporter inhibitor Atomoxetine capsules 10 mg or 18 mg Three times a day
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	0	1
Overall Study Physician Decision	0	1

Baseline Characteristics

Norepinephrine Transporter Blockade, Autonomic Failure (NETAF)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=40 Participants All participants were randomized to receive all interventions. All participants received Atomoxetine and All participants received Placebo. Participants were randomized, double blinded, In Phase I (0-4 weeks), Day 0-Day 28, Day 0 is baseline: 50 % of participants got Atomoxetine (active drug) 50 % of participants got Placebo In Phase II Day 36 to Day 64. Participants were washed out of Phase I Participants who received Atomoxetine at phase 1, got Placebo in Phase II Participants who received Placebo at Phase 1, got Atomoxetine in Phase II
Age, Continuous	67.9 years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	40 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Weight	80 Kg STANDARD_DEVIATION 18 • n=5 Participants
Height	174.7 cm STANDARD_DEVIATION 9.9 • n=5 Participants
BMI (Body Mass Index)	26.2 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants
Diagnosis 2 Multiple System Atrophy (MSA)	18 Participants n=5 Participants
Diagnosis 2 Non MSA (Parkinson disease or Pure autonomic failure	22 Participants n=5 Participants
To identify Atomoxetine Responders High Concentration responders -Atomoxetine 18mg	10 Participants n=5 Participants
To identify Atomoxetine Responders Low Concentration responders with Atomoxetine 10mg	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: week 0 to week 4

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo	Atomoxetin n=36 Participants Atomoxetine: norepinephrine transporter inhibitor Atomoxetine capsules 10 mg or 18 mg
Change in the OHQ (Orthostatic Hypotension Questionnaire) Composite Score OHQ composite score at Baseline	4.61 Score on a scale Standard Deviation 2.16	4.17 Score on a scale Standard Deviation 2.29
Change in the OHQ (Orthostatic Hypotension Questionnaire) Composite Score OHQ composite score at 4weeks	3.35 Score on a scale Standard Deviation 1.98	3.5 Score on a scale Standard Deviation 2.25
Change in the OHQ (Orthostatic Hypotension Questionnaire) Composite Score Difference in OHQ composite score at 4 weeks	-0.58 Score on a scale Standard Deviation 2.39	-0.5 Score on a scale Standard Deviation 1.58

SECONDARY outcome

Timeframe: Baseline to 4 weeks

Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) (measured in mm of Hg) , is recorded after 10 mins of standing. The changes SBP and DBP are compared from baseline, post drug (4 weeks)

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo	Atomoxetin n=36 Participants Atomoxetine: norepinephrine transporter inhibitor Atomoxetine capsules 10 mg or 18 mg
Change in Blood Pressure difference increase in SBP; post drug 4 weeks; standing for 10 mins	3.88 mm of Hg Standard Deviation 19.83	-2.44 mm of Hg Standard Deviation 23.54
Change in Blood Pressure DBP;post drug; standing 10 mins at 4 weeks	-3.06 mm of Hg Standard Deviation 15.85	-0.94 mm of Hg Standard Deviation 15.6

SECONDARY outcome

Timeframe: Baseline and at 4 weeks

HR is compared to baseline after 10 mins of standing. The difference increase in Heart rate from baseline, post drug at 4 weeks

Outcome measures

Outcome measures
Measure	Placebo n=38 Participants Placebo	Atomoxetin n=36 Participants Atomoxetine: norepinephrine transporter inhibitor Atomoxetine capsules 10 mg or 18 mg
Change in Heart Rate (HR)	79.12 Beats per minute Standard Deviation 11.83	82.68 Beats per minute Standard Deviation 14.58

Adverse Events

Dose Optimization Phase

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Atomoxetine

Serious events: 2 serious events

Other events: 13 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Dose Optimization Phase n=48 participants at risk -1 to -10 days Open-label, dose-optimization phase: To test two doses of Atomoxetine (10,18 mg), until they met criteria for Atomoxetine Responders. total of 48 participated in this phase. 40 participants were qualified as Atomoxetine responders.	Placebo n=40 participants at risk Double blind Placebo group Overall subjects who received placebo capsules	Atomoxetine n=40 participants at risk Double blind Atomoxetine 18 mg or Atomoxetine 10 mg. Depending upon the dose the participant qualified as Atomoxetine Responders. Subjects received atomoxetine capsules 18 mg or 10 mg three times a day. The dose stratification was not done Majority of the subjects received 18 mg of Atomoxetine three times a day .
Infections and infestations Patient hospitalized after found in bed disoriented and confused with fever of unknown origin	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Gastrointestinal disorders Trouble swallowing	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Gastrointestinal disorders Bowel Obstruction	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.

Other adverse events

Other adverse events
Measure	Dose Optimization Phase n=48 participants at risk -1 to -10 days Open-label, dose-optimization phase: To test two doses of Atomoxetine (10,18 mg), until they met criteria for Atomoxetine Responders. total of 48 participated in this phase. 40 participants were qualified as Atomoxetine responders.	Placebo n=40 participants at risk Double blind Placebo group Overall subjects who received placebo capsules	Atomoxetine n=40 participants at risk Double blind Atomoxetine 18 mg or Atomoxetine 10 mg. Depending upon the dose the participant qualified as Atomoxetine Responders. Subjects received atomoxetine capsules 18 mg or 10 mg three times a day. The dose stratification was not done Majority of the subjects received 18 mg of Atomoxetine three times a day .
Nervous system disorders Headache	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	7.5% 3/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Psychiatric disorders Insomnia	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Gastrointestinal disorders Reflux esophagitis	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	5.0% 2/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Renal and urinary disorders Urinary tract infection	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	7.5% 3/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Respiratory, thoracic and mediastinal disorders upper respiratory infections	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	12.5% 5/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Nervous system disorders altered sensation, tingling, numbness , cold	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	7.5% 3/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	12.5% 5/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Gastrointestinal disorders Altered bowel movements	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	5.0% 2/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Renal and urinary disorders Prostatitis	2.1% 1/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Skin and subcutaneous tissue disorders Rash	2.1% 1/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	0.00% 0/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.
Injury, poisoning and procedural complications Injury related to fall	0.00% 0/48 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	5.0% 2/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.	2.5% 1/40 • Day -10 to Day 64 of the study The adverse events (AEs) were noted after the subjects signed the Consent. Among all AEs : 2 happened in dose optimization period, 23 were recorded in phase of Atomoxetine treatment and 20 were in phase of Placebo treatment.

Additional Information

Dr Cyndya Shibao

Vanderbilt University Medical center

Phone: 615-322-2318

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place