A Study of Norepinephrine in Patients With Congenital Insensitivity to Pain and Anhidrosis

NCT02624310 | Withdrawn Phase 2

• 1 other identifier: 14-01774
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of this study is to increase norepinephrine levels in a population of young adults where NE levels are very low or undetectable. In order to achieve this, the optimal dose will be determined in a titration step. In the titration step, different doses of L-DOPS will be tested in order to find the optimal and safest dose suitable for each individual enrolled in the study. Because L-DOPS has never been used in the US in children or young adults, with this titration step investigators will also determine the safest dose for this population. Currently, L-DOPS is being used in our center to treat othostatic hypotension in autonomic failure. The titration step for this study starts with the dose of 100 mg and increases in an escalating manner up to a maximum of 600 mg a day (see investigational brochure attached). L-DOPS has been developed in capsules for oral used and all the previous safety data has been performed using this route. Oral route is the one that will used during study. Carbidopa is well tolerated, safe in children and it has been used in this population in the US without severe adverse effects.

Conditions

HSAN Type IV

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Safety and tolerability will be assessed using general physical and neurological examinations, vital signs including blood pressure and heart rate, temperature and body weight, blood chemistries including serum creatinine, electrolytes, transaminases and liver function tests, 12 lead electrocardiograms and adverse events monitoring.

  8 weeks

Study Arms (2)

Droxidopa First, Placebo Second

EXPERIMENTAL

Participants in this arm will receive droxidopa first, then cross over and receive placebo

Drug: Droxidopa (L-DOPS); Drug: Placebo

Placebo First, Droxidopa Second

EXPERIMENTAL

Participants in this arm will receive placebo first, then cross over and receive droxidopa

Drug: Droxidopa (L-DOPS); Drug: Placebo

Interventions

Droxidopa (L-DOPS) DRUG

Patients will be given their initial 100 mg of L-DOPS (visit 2a). The dose of L-DOPS will be increased in escalation in the following visits. Each day the dose will be increased 100 mg. The escalating doses of L-DOPS will be 200 mg (visit 2b), 300 mg (visit 2c), 400 mg (visit 2d), 500 mg (visit 2e) and 600 mg (visit 2f). Following this titration step, L-DOPS will be withdrawn from the subjects for a minimum of two weeks, when the subject will return for visit 3.Visit 3a,b,c,d,e,f: Carbidopa open-label dose titration. This titration step will be similar than L-DOPS titration. Carbidopa starting dose will be 100 mg (visit 3a) and will be increased 100 mg each visit up to a maximum of 600 mg (visit 3f). Following carbidopa titration step, patients will be withdrawn from the drug for minimum of two weeks, then the subject will return for the next titration step (visit 4).

Also known as: Northera

Droxidopa First, Placebo Second; Placebo First, Droxidopa Second

Placebo DRUG

Droxidopa First, Placebo Second; Placebo First, Droxidopa Second

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female 15 years old or older
• Patient carrying the genetic mutation for the NTRK1 gene
• Patients (or guardian if patient it is underage) have signed a written consent to participate in the study after being fully informed about the procedure of the study and their right to withdraw at anytime during it.

You may not qualify if:

• Patients taking amphetamines, norepinephrine reuptake inhibitors.
• Patients taking any medication that can interact with the study drug L- DOPS.
• Patients with previous severe hypertension (systolic blood pressure \>170 mmHg)
• Patients with arrhythmias or any other cardiac condition.
• Women who are pregnant or breast feeding
• Have a renal or hepatic disease

Sponsors & Collaborators

• NYU Langone Health: lead

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: December 8, 2015
• Study Start: January 1, 2016
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2019
• Last Updated: September 12, 2016

Record last verified: 2016-09