Exercise Versus DDAVP in Patients With Mild Hemophilia A
Condition: Hemophilia A
MeSH terms: Hemophilia A
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): DDAVP Inhalant Product; Exercise Intervention
Intervention type(s): Drug; Behavioral
Intervention description(s): 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.; 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.
Other intervention name(s): IN DDAVP
Intervention MeSH terms: Deamino Arginine Vasopressin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment