Provide proof-of-concept for the hypothesis that guanfacine diminishes cognitive side-effects in ER+ BC patients treated with adjuvant hormonal therapy. Secondary, provide data for power calculations in later studies.
ID
Source
Brief title
Condition
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in cognitive functions from placebo to guanfacine condition. Cognitive
functions are assessed by standardized neuropsychological tasks and include
executive functions, attention, memory, and processing speed.
Secondary outcome
Change in depression / anxiety and physical side-effects from placebo to
guanfacine condition. Affect is measured by a standardized questionnaire
(POMS). Physical side-effects recorded include those reported for tamoxifen and
guanfacine. The most commonly reported side effects for tamoxifen (hot flushes,
vaginal bleeding and secretions, pruritus vulvae) and guanfacine (sedation,
headache, abdominal pains, signs and symptoms related to changes in blood
pressure) are explicitly asked about during a weekly structured telephone
interview.
Background summary
Following primary treatment, Estradiol Receptor positive (ER+) Breast Cancer
(BC) is usually treated with adjuvant hormone therapy. The latter consists of
Tamoxifen or Aromatase Inhibitors (AI). Apart from hormonal side-effects,
cognitive and affective side-effects are also reported, a finding that is
supported by neuropsychological research. These effects probably stem from
interactions with sex hormone receptors in the brain. Guanfacine is a
noradrenergic alpha2A agonist, that has been shown to improve catecholaminergic
Prefrontal Cortex (PFC) network connections. Therefore, it was hypothesized
that guanfacine will have a positive effect on cognitive/affective side effects
of adjuvant hormonal treatment.
Study objective
Provide proof-of-concept for the hypothesis that guanfacine diminishes
cognitive side-effects in ER+ BC patients treated with adjuvant hormonal
therapy. Secondary, provide data for power calculations in later studies.
Study design
Double-blind placebo-controlled cross-over
Intervention
Guanfacine, 0.03-047. mg/kg (2 or 3 mg) once daily, for four consecutive weeks,
and placebo during four weeks. Note that all participants are on stable 20 mg
daily Tamoxifen treatment, on inclusion, after completion and during all study
conditions.
Study burden and risks
The burden associated with the study consists of a screening and baseline
visit, including blood sampling and 1-hour cognitive testing. Blood sampling
and cognitive testing are repeated on two other visits. Finally, a weekly
telephone interview on physical side-effects. Risks are those associated with
guanfacine intake, which are well-known and closely monitored.
Louis Armstrongweg 78
Almere 1311RL
NL
Louis Armstrongweg 78
Almere 1311RL
NL
Listed location countries
Age
Inclusion criteria
• treated with adjuvant tamoxifen therapy for ER receptor-positive Breast Cancer
• on tamoxifen treatment for 3-18 months, 20 mg stable dosing for at least a month
• postmenopausal
• subjective complaints of cognitive side effects
• weight between 50 and 90 kg
• 20 <= BMI <= 27
• fluent in Dutch
• normal (or corrected-to-normal) vision
• normal dexterity
Exclusion criteria
• prior exposure to chemotherapy
• diagnosis of prior or existing cardiovascular, neurological or psychiatric disorder that may influence sensitivity to guanfacine or study endpoint(s)
• contraindications for guanfacine (hypotension, bradycardia, syncope, extended QT interval)
• (prior) diagnosis of ADHD
• use of clonidine or other anti-hypertensive agents
• use of drugs with a strong influence on CYP2D6, CYP3A4/5 (e.g., ketoconazole, carbamazepine)
• use of SSRIs and other antidepressants
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-000506-11-NL |
| CCMO | NL56785.072.16 |