Recruiting

DDAVP vs. ExerciseDDAVP vs. Exercise in Patients With Mild Hemophilia A

Sponsor:

The Hospital for Sick Children

Code:

NCT03136003

Conditions

Mild Haemophilia A Without Inhibitor

Eligibility Criteria

Sex: Male

Age: 13 - 21

Healthy Volunteers: Not accepted

Interventions

DDAVP

Exercise

Study Details

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.

Conditions

Mild Haemophilia A Without Inhibitor

Study ID

NCT03136003

Start date

Jul 4, 2017

Status verified date

Nov, 2017

Completion date

Aug, 2018

Anticipated

Primary completion date

Aug, 2018

Anticipated

Eligibility Criteria

Sex: Male

Age: 13 - 21

Healthy Volunteers: Not accepted

Inclusion Criteria:

Patients ≥13 years of age and ≤21 years of age with Mild Hemophilia A (MHA), with a historical baseline FVIII:C level of ≥5% to ≤40% followed at either the Hospital for Sick Children or St. Michael's Hospital (Toronto).
Patients ≥13 years of age and ≤21 years of age with genetically confirmed Mild Hemophilia A (MHA), with FVIII:C level of ≥5% to ≤50% followed at either the Hospital for Sick Children or St. Michael's Hospital (Toronto).

Exclusion Criteria:

A currently circulating or history of a previous inhibitor ( ≥0.5 BU) within the past 5 years. As inhibitor development in MHA is rare, it is not expected that any patient will be excluded for this reason.
Any FVIII infusion or DDAVP use in the preceding week. This is to avoid an residual FVIII still being present in a patient who has taken an extended half-life FVIII.
Co-existence of a congenital bleeding disorder other than MHA (e.g. VWD).
Prior history of coronary artery disease or pulmonary disease, severe arthropathy interfering with ability to exercise.
Patients on beta-blockers, anti-platelet agents or regular non-steroidal anti-inflammatory medications (e.g. Celebrex).
Patients with an active infectious or inflammatory condition. This includes HIV, active hepatitis B or C as reflected in elevated AST, ALT, RNA positivity for hepatitis B or C.
Patients who are active (defined as smoking daily) smokers (cigarettes, marijuana). This exclusion is put into place as we do not know if daily smoking will impact on the hemostatic response to either exercise or DDAVP.
Patients with limited exercise tolerance for any reason.
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.
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).

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: DDAVP followed by exercise

Intervention #1: DDAVP. 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).

Intervention #2: Exercise

active comparator: Arm B: DDAVP alone

experimental: Arm C: Exercise alone

Intervention #1: Exercise

Intervention #2: no further intervention (rest)

experimental: ARM D: Exercise followed by DDAVP

Intervention #1: Exercise

Intervention #2: DDAVP. 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).

Interventions

DDAVP

The participant will take either 1 or 2 nasal sprays of IN DDAVP (known as Octostim® in Canada). After receiving IN DDAVP, the participant will rest for 30 minutes.

Exercise

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 dependent on their height. The workload is increased every minute in standard increments also based on the participant's height. All participants will exercise until they complete 3-minutes of cycling at 85% of their maximum predicted heart rate or exhaustion (whichever is first). Upon completion of planned exercise, work load is decreased to zero watts and participants will continue cycling at this cool-down rate for an additional 3-minutes, before getting off the ergometer.

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Manuel Carcao

416-813-7654 manuel.carcao@sickkids.ca

Patrick Ng

416-813-2145 patrick.ng@sickkids.ca

Locations

The Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G1X8

Principal Investigator:

Manuel Carcao

More Information

Sponsor

The Hospital for Sick Children

Last update posted

Dec 4, 2017

Last verified

Nov, 2017

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by The Hospital for Sick Children on 2017-12-04.