The Oslo Study of Clonidine in Elderly Patients With Delirium (LUCID)

Delirium ("acute confusional state")is characterized by an acute decline in attention and cognition, and is a common clinical syndrome in elderly patients.

The purpose of this randomised, controlled, parallel group pilot trial is to explore superiority of clonidine vs placebo in decreasing delirium in patients diagnosed delirium at the acute geriatric ward.

We will also study the feasibility of oral clonidine in a geriatric ward and effects of clonidine upon a variety of outcomes as a means to design a more definite study later.

Study Overview

• Status: Terminated
• Conditions: Delirium
• Intervention / Treatment: Drug: Placebo; Drug: Clonidine

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, N-0424
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient > 65 years old admitted to the Medical department
• Delirium or subsyndromal delirium diagnosed within the last 48 hours
• Signed informed consent from patient or relatives
• Expected cooperation of the patients for the treatment and follow up

Exclusion Criteria:

• Symptomatic bradycardia, bradycardia due to sick-sinus-syndrome, second- or third- degree AV-block (not treated With pacemaker) or any other reason causing HR <50 bpm at time of inclusion
• Symptomatic hypotension or orthostatic hypotension, or a systolic BP <120 at the time of inclusion
• Ischemic stroke within the last 3 months or critical peripheral ischemia
• Acute coronary syndrome, unstable or severe coronary heart disease (symptoms at minimal physical activity; NYHA 3 and 4) and moderate to severe heart failure (NYHA 3 and 4).
• A diagnosis of polyneuropathy or pheochromocytoma
• Renal insufficiency (estimated GFR<30 ml/min according to the MDRD formula).
• Body weight < 45 kg.
• Considered as moribund on admission.
• Not able to take oral medications
• Current use of tricyclic antidepressants, monoamine reuptake inhibitors or ciclosporin
• Previously included in this study
• Adverse reactions to clonidine or excipients (lactose, saccharose)
• Not speaking or reading Norwegian
• Any other condition as evaluated by the treating physician
• Admitted to the ICU

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clonidine; Clonidine administered orally: Day 1/loading doses: 75µg every 3rd hour until maximum 4 doses. Day 2-7/maintenance doses: 75µg BID. Duration of treatment is maximum 7 days.	Drug: Clonidine
Placebo Comparator: Placebo (sugar pill); Placebo administered orally (identical capsula as for expirimental drug): Day 1/loading doases: 75µg every 3rd hour until maximum 4 doses. Day 2-7/maintenance doses: 75µg BID. Duration of treatment is maximum 7 days.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
MDAS (Memorial delirium assessment scale)	Participants will be followed for the duration of hospital stay, an expected average of approximately 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-first delirium	We will compare the actively treated group with the placebo group (also with subanalyses for subsyndromal delirium and hypoactive/ hyperactive/ mixed delirium) with respect to: • time to first resolution, monitored by DSM-5 criteria	2 weeks
Incidence of "full-scale" delirium	• monitored by DSM-5 criteria	2 weeks
Severity of delirium	measured by MDAS, OSLA	2 weeks
Delirium subtype	Measured by MDAS, OSLA	2 weeks
The use of "rescue medication"		2 weeks
Length of hospital stay		Hospital stay
Patient distress		2 weeks
Side effects of clonidine		4 months
Pharmacokinetic response to clonidine		1 week
Pharmacodynamic response to clonidine		2 weeks
Biomarkers		2 weeks
Institutionalization		4 months
Survival		4 months
Cognitive function/ independence		4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exposure-response analyses	We will also do per protocol analyses and exposure-response analyses based on measurements of the plasma concentration of clonidine	4 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Torgeir Bruun Wyller, MD PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Hov KR, Neerland BE, Andersen AM, Undseth O, Wyller VB, MacLullich AMJ, Skovlund E, Qvigstad E, Wyller TB. The use of clonidine in elderly patients with delirium; pharmacokinetics and hemodynamic responses. BMC Pharmacol Toxicol. 2018 Jun 8;19(1):29. doi: 10.1186/s40360-018-0218-1.
• Neerland BE, Hov KR, Bruun Wyller V, Qvigstad E, Skovlund E, MacLullich AM, Bruun Wyller T. The protocol of the Oslo Study of Clonidine in Elderly Patients with Delirium; LUCID: a randomised placebo-controlled trial. BMC Geriatr. 2015 Feb 10;15:7. doi: 10.1186/s12877-015-0006-3.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2014
• Primary Completion (Actual): September 12, 2017
• Study Completion (Actual): September 12, 2017

Study Registration Dates

• First Submitted: September 25, 2013
• First Submitted That Met QC Criteria: October 7, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): October 31, 2018
• Last Update Submitted That Met QC Criteria: October 29, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: 2013-000815-26 (EudraCT Number)