Exercise Versus DDAVP in Patients With Mild Hemophilia A

NCT03379974 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: IRB17-00290
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

Individuals with mild hemophilia A (MHA) bleed infrequently but can in the setting of trauma which often is when participating in sports/exercise. Although both exercise and DDAVP (desmopressin) can raise Factor 8/Von Willebrand Factor (FVIII/VWF levels), it is not clear whether the pathophysiological mechanism is the same. Consequently it is not known if DDAVP and exercise would have additive effects in raising FVIII:C and VWF levels or if one would one negate the effect of the other. The aim of this 2 center (Sickkids and Nationwide Children's), prospective, cross-over design study is to compare the impact of exercise vs. DDAVP on hemostasis in patients with MHA and also to investigate the impact of sequentially administering these interventions on their hemostatic indices.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• •Factor 8 level after exercise [ Time Frame: Baseline, 30 min post intervention #1, 30 min post intervention #2 and 90 minute post intervention #2

  To compare the increase in FVIII:C (measured as absolute and fold increase) associated with a standardized moderate intensity aerobic exercise regimen (3-minutes of exercise at 85% of the predicted maximum heart rate) to intranasal DDAVP in post-adolescent males with MHA

  Baseline, 30 min post intervention #1, 30 min post intervention #2 and 90 minute post intervention #2

Secondary Outcomes (2)

• •Factor 8 level after sequential administration of exercise followed by IN DDAVP (or vice versa) [ Time Frame: Baseline, 30 min post intervention #1, 30 min post intervention #2 and 90 minute post intervention

  Baseline, 30 min post intervention #1, 30 min post intervention #2 and 90 minute post intervention

• •Associations between baseline physical activity scores and Factor 8 levels after exercise [ Time Frame: Baseline, 30 min post intervention #1, 30 min post intervention #2 and 90 minute post intervention

  Baseline, 30 min post intervention #1, 30 min post intervention #2 and 90 minute post intervention

Study Arms (4)

ARM A: DDAVP followed by exercise

EXPERIMENTAL

1. Intervention #1: DDAVP Inhalant Product intervention The participant will take either 1 or 2 nasal sprays of IN DDAVP. For patients weighing \<50 kg: 150 ug (i.e. 1 spray into one nostril) and patients weighing ≥50 kg: 300 ug (i.e. 2 sprays - one into each nostril). 2. Intervention #2: Exercise intervention

Drug: DDAVP Inhalant Product; Behavioral: Exercise Intervention

ARM B: DDAVP alone

ACTIVE COMPARATOR

1. Intervention #1: DDAVP Inhalant Product intervention The participant will take either 1 or 2 nasal sprays of IN DDAVP. For patients weighing \<50 kg: 150 ug (i.e. 1 spray into one nostril) and patients weighing ≥50 kg: 300 ug (i.e. 2 sprays - one into each nostril). 2. Intervention #2: no further intervention (rest)

Drug: DDAVP Inhalant Product

ARM C: Exercise intervention

EXPERIMENTAL

1. Intervention #1: Exercise intervention 2. Intervention #2: no further intervention (rest)

Behavioral: Exercise Intervention

ARM D: Exercise followed by DDAVP

EXPERIMENTAL

1. Intervention #1: Exercise intervention 2. Intervention #2: DDAVP Inhalant Product intervention The participant will take either 1 or 2 nasal sprays of IN DDAVP. For patients weighing \<50 kg: 150 ug (i.e. 1 spray into one nostril) and patients weighing ≥50 kg: 300 ug (i.e. 2 sprays - one into each nostril).

Drug: DDAVP Inhalant Product; Behavioral: Exercise Intervention

Interventions

DDAVP Inhalant Product DRUG

For the DDAVP intervention the participant will take either 1 or 2 nasal sprays of IN DDAVP. After receiving IN DDAVP, the participant will rest for 30 minutes.

Also known as: IN DDAVP

ARM A: DDAVP followed by exercise; ARM B: DDAVP alone; ARM D: Exercise followed by DDAVP

Exercise Intervention BEHAVIORAL

For the exercise intervention the participant will exercise on a stationary cycle-ergometer using the previously-validated, progressively-incremental Godfrey protocol. Per the Godfrey protocol, the participant starts cycling on the calibrated cycle-ergometer with an initial exercise load that is dependent on their height. The workload is increased every minute in standard increments also based on the participant's height. All participants will exercise till they complete 3-minutes of cycling at 85% of their maximum predicted heart rate or till exhaustion (whichever comes first). Upon completion of planned exercise, work load will be decreased to zero watts and participants will be instructed to continue cycling at this cool-down rate for additional 3-minutes, before getting of the ergometer.

ARM A: DDAVP followed by exercise; ARM C: Exercise intervention; ARM D: Exercise followed by DDAVP

Eligibility Criteria

• Age: 13 Years - 21 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• \) Patients of ≥13 years of age and ≤21 years of age with MHA (FVIII:C level of ≥6% to ≤50%).

You may not qualify if:

• A currently circulating or a history of inhibitor (0.5 BU on two or more occasions). Inhibitor development is rare in MHA.
• History of FVIII infusion (both standard-acting and extended half-life products) or DDAVP use in preceding 1 week. Patients will be instructed to hold factor use or DDAVP for 1-week prior to participation in study, except for management of acute bleeds, in which case they will be instructed to inform the PI via telephone or e-mail.
• Patients with severe arthropathy (as determined by the principal investigator) interfering with ability to exercise. Severe arthropathy is rare in MHA.
• Patients on beta-blockers, anti-platelet agents or regular non-steroidal anti-inflammatory medications (e.g. Celebrex).
• Patients who are active smokers (cigarettes, marijuana).
• Patients with a history of a recent bleed (in preceding 2 weeks) in any location or a joint/muscle bleed in the lower limbs in the preceding 4 weeks.
• Co-existence of a congenital bleeding disorder other than MHA (e.g. VWD).
• Patients with an active infectious or inflammatory condition. This includes previously identified HIV, active hepatitis B or C as reflected in elevated AST, ALT, RNA positivity for hepatitis B or C. HIV, hepatitis B and C are very rare in the age group (13-21 years) we hope to accrue in the proposed study.
• Patients who for medical reasons should not receive DDAVP \[those with renal or CNS disease (e.g. brain tumor)\] or have previously experienced adverse events with DDAVP (e.g. hypotensive event, seizure).

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• The Hospital for Sick Children: collaborator

Study Sites (4)

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Deamino Arginine Vasopressin

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Riten Kumar, MD, MSc

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The randomization of the participant to a study arm will be done prior to the study visit by the pharmacy at the hospital. The Investigator and study team will know the arm each participant is in before the patient's visit. This information will also be provided to the participant before the visit.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: December 20, 2017
• Study Start: July 31, 2018
• Primary Completion: August 30, 2019
• Study Completion: December 5, 2019
• Last Updated: February 25, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will share

Locations

US (4)