DDAVP vs. Exercise in Patients With Mild Hemophilia A

NCT03136003 | Unknown Phase 4 DMC

• 1 other identifier: 1000054948
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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

Outcome Measures

Primary Outcomes (1)

• Factor 8 level after exercise

  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.

  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)

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

• Associations between baseline physical activity scores and Factor 8 levels after exercise

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

Study Arms (4)

Arm A: DDAVP followed by exercise

EXPERIMENTAL

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

Drug: DDAVP; Behavioral: Exercise

Arm B: DDAVP alone

ACTIVE COMPARATOR

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: no further intervention (rest)

Drug: DDAVP

Arm C: Exercise alone

EXPERIMENTAL

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

Behavioral: Exercise

ARM D: Exercise followed by DDAVP

EXPERIMENTAL

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).

Drug: DDAVP; Behavioral: Exercise

Interventions

DDAVP DRUG

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.

Also known as: IN DDAVP, Octostim

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

Exercise BEHAVIORAL

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.

ARM D: Exercise followed by DDAVP; Arm A: DDAVP followed by exercise; Arm C: Exercise alone

Eligibility Criteria

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

You may qualify if:

• 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).

You may not qualify if:

• 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 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).

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Canadian Hemophilia Society: collaborator
• Unity Health Toronto: collaborator
• Nationwide Children's Hospital: collaborator

Study Sites (2)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

NOT YET RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

RECRUITING

MeSH Terms

Interventions

Deamino Arginine Vasopressin; Exercise

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; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Manuel Carcao

  Staff Haematologist

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manuel Carcao

CONTACT

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

Patrick Ng

CONTACT

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

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: PRINCIPAL INVESTIGATOR
• PI Title: Hematologist

Study Record Dates

• First Submitted: April 27, 2017
• First Posted: May 2, 2017
• Study Start: July 4, 2017
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: December 4, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will share

Locations

CA (2)