NCT03379974

Exercise Versus DDAVP in Patients With Mild Hemophilia A

Exercise Versus DDAVP in Patients With Mild Hemophilia A - is One Non-inferior to the Other and do They Work Additively in Improving Hemostasis?

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Nationwide Children's Hospital · Academic / Other
• Sex: Male
• Age: 13 Years – 21 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Persons with mild hemophilia A (MHA) (defined as having a FVIII level of \>5% to ≈50%) bleed infrequently but can in the setting of trauma which can often is in the context of participating in sports/exercise. FVIII levels temporarily rise with stress, exercise and with DDAVP (1-desamino-8-Darginine vasopressin, desmopressin). In the case of DDAVP, the Hospital for Sick Children (SickKids) Hemophilia Team and others have shown that FVIII and VWF levels rise by 2-4 fold with DDAVP. Consequently many persons with MHA in an attempt to reduce their risk of bleeding take intranasal (IN) DDAVP prior to sports activities/exercise. IN DDAVP is reasonably expensive ($300/bottle of Octistim® in Canada and $700/bottle of Stimate® in USA), requires fluid restriction, and may be associated with nausea, vomiting, seizures and tachyphylaxis. Recently, our group completed a pilot/feasibility study to evaluate the impact of a prescribed, moderate intensity aerobic exercise regimen on hemostatic indices in 30 children with hemophilia A \[HA\] or B \[HB\] (all severities) and documented a significant improvement in multiple coagulation parameters (platelet count, FVIII:C and von Willebrand factor \[VWF\]) with exercise. This improvement was particularly pronounced in 13 post-adolescent males with mild-moderate HA. In this sub-cohort, the investigators noted a mean 2.3 fold increase in FVIII:C immediately after exercise, which remained significantly elevated at 1.9 fold,1 hour after completion of exercise These changes in hemostatic variables associated with aerobic exercise may be protective against bleeding, and may negate the need to administer IN DDAVP immediately prior to sports participation. Although both exercise and DDAVP can raise FVIII/VWF levels, it is not clear whether the pathophysiological mechanism in which they do this is the same. Consequently it is not known if DDAVP and exercise would augment each other's effects in raising FVIII:C and VWF levels or if one would one negate the effect of the other. Herein, the investigators propose a prospective, interventional study of exercise vs IN DDAVP in 40-50 post adolescent (13-21 yr) males with MHA to compare their impact on hemostasis and also to investigate the impact of sequentially administering these interventions on hemostatic indices.

Conditions

• Hemophilia A

Interventions

Type	Name	Description
DRUG	DDAVP Inhalant Product	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.
BEHAVIORAL	Exercise Intervention	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.

Timeline

• Start date: 2018-07-31
• Primary completion: 2019-08-30
• Completion: 2019-12-05
• First posted: 2017-12-20
• Last updated: 2020-02-25

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study