Clinical Trial: DDAVP vs. Exercise

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: DDAVP vs Exercise in Patients With Mild Hemophilia A - Which is Better and do They Work Synergistically in Improving Hemostasis?

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 Columbus, Ohio), 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 Summary:

Persons with mild hemophilia A (MHA) (defined as having a FVIII level of >5% to ≈40%) 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, we 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 pathophysi
Sponsor: The Hospital for Sick Children

Current Primary Outcome: 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 Factor 8 levels (FVIII:C) (measured as absolute and fold increase) associated with moderate intensity aerobic exercise (approximately 15 minutes of gradually increasing aerobic exercise culminating in 3-minutes of exercise at 85% of the predicted maximum heart rate) vs. IN DDAVP in post-adolescent males with MHA.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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#2 ]
    To determine the absolute and fold increase in Factor 8 levels (FVIII:C) associated with the sequential administration of exercise followed by IN DDAVP (or vice versa).
  • 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#2 ]
    To explore the impact of baseline physical activity (measured using the International Physical Activity Questionnaire [IPAQ]-short form) on exercise induced increase in Factor 8 levels (FVIII:C).


Original Secondary Outcome: Same as current

Information By: The Hospital for Sick Children

Dates:
Date Received: April 27, 2017
Date Started: June 2017
Date Completion: August 2018
Last Updated: April 27, 2017
Last Verified: April 2017