Clinical trial NCT00388128: Caffeine and Intermittent Claudication
Official title: Effects of Caffeine in Patients With Intermittent Claudication.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Intermittent Claudication
Keywords: Intermittent Claudication
PAD
Caffeine
Walking capacity
ABI
QoL
Growth factor
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Herning Hospital
name: Central Jutland Regional Hospital
First posted: 2006-10-13
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the change in Walking capacity after an intake of caffeine. The study design is cross-over and follow-up of 80 patients with leg pain caused by narrowing of their leg arteries, Peripheral Vascular Disease (PAD), stage II. Half of all will be revascularised, follow up will be after 3 months. It is hypothesized that caffeine (6mg/kg) can be a cheap, safe drug before walking exercise. Primary endpoint is maximum walking distance (MWD), treadmill-testing,(constant load, 0%,2m/h). Secondary endpoints are pain free walking distance (PWD), maximum muscle strength, endurance, reaction speed, balance, cognitive function, health related quality of life (SF-36).

Detailed description: PAD has a prevalence of 15-20 % in an elderly (\>50) western population. PAD can not be seen in isolation but represents the peripheral manifestation of a generalized artherosclerosis. The co-morbidity with coronary or cerebralartherosclerosis depends on the degree of severity of PAD, the relative risk of a death (predominantly cardiac) is increased by a factor 4. From af medical and a socio-economic point of view there is the need to control the PAD complication rate and related treatment costs as effectively as possible.

The aim of any treatment of intermittent claudication is a clinically relevant improvement in the patient´s mobility and quality of life.

There is agreement, that physical training does improve the collateralisation of vascular lesions, the rheologic properties of blood and lead to a shift from glycolytic to oxidative muscle fibers in the working musculature which increases the capillary density. The effect of physical training is also to modify the patients risk factor profile, even moderate training increase the insulin receptor sensitivity and the fibrinolytic activity and decrease the dLDL/HDL ratio and the diastolic blood pressure in hypertensive patients - and thereby decrease the overall cardiac mortality.

This is a Phase 3, 12-week, double-blind, randomized, placebo-controlled cross-over and a follow-up study with 80 patients with intermittent claudication, half of which will be revascularized.

The objectives of this study are to evaluate the efficacy of caffeine (6mg/kg)and the revascularisation procedure. The primary end-point will be maximal walking distance (MWD) in both groups of patients. Other efficacy measures will include claudication onset time (PWD), changes in Ankle Brachial Index (ABI), Quality of Life (QoL), cognitive function, plasma response of Vascular Endothelian Growth Factor (VEGF, FGF). Safety variables will include routine hematology parameters and adverse events.

Eligibility criteria: Inclusion Criteria:

* men and women \> 40 years
* history of IC of the lower extremities, Fontaine II
* ankle-brachial index (ABI)\> 0.9 (subjects who are referred for a revasularizarition procedure)

Exclusion Criteria:

* dementia
* diabetes
* illness or reason to be unable to participate, f.ex. general weakness, amputation or arthritis
* acute illness, f.ex. inflammation, unstable angina
* other reasons which contraindicate participation/treadmill exercise
* intake of Trental and/or Teofyllamin
* weight \> 100kg

Primary outcomes:
measure: Quality of life
timeFrame: during test 1 and 3
measure: Maximum walking distance
timeFrame: during treadmill test
Secondary outcomes:
measure: Painfree Walking Distance
timeFrame: treadmill test
measure: Max muscle strength (MVC) of kneeextension
timeFrame: At end of each test
measure: Endurance of 50%MVC kneeextension
timeFrame: At end of each test
measure: Postural stability
timeFrame: in all tests
measure: Reaction speed
timeFrame: in all tests
measure: Cognitive function
timeFrame: in all tests
measure: Walking Impairment Questionnaire
timeFrame: in first and third test
measure: vascular endothelian growth factors VGF. FGF
timeFrame: before and after 1. and 2. test
Other outcomes:
Locations:
city: Herning
country: Denmark
facility: Herning Hospital, Surgical research dep.
state: Region Central-Jutland
Study officials:
affiliation: Herning Hospital
name: Anne-Mette H Momsen, MPH, Phys, ph.D stud
role: PRINCIPAL_INVESTIGATOR
References:
citation: Momsen AH, Jensen MB, Norager CB, Madsen MR, Vestersgaard-Andersen T, Lindholt JS. Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication. Br J Surg. 2010 Oct;97(10):1503-10. doi: 10.1002/bjs.7149.