AEIPDT: Efficacy of Aerobic Exercise Added to Alprazolam in Panic Disorder Treatment

• Sponsor: University of Buenos Aires (Other)
• Overall Status: Completed
• CT.gov ID: NCT00803400
• Collaborator: (none)
• Enrollment: 150
• Location: 1
• Arms: 2
• Actual Duration (Months): 12
• Patients Per Site Per Month: 12.5

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the combination of aerobic physical exercise and alprazolam in patients with panic disorder has a better therapeutic response than the treatment with alprazolam alone.

Condition or Disease	Intervention/Treatment	Phase
Panic Disorder	Drug: Alprazolam; Drug: Alprazolam + Aerobic exercise	Phase 4

Detailed Description

We have observed in our clinical practice that patients who practiced aerobic physical exercise had faster remissions and better improvement in their treatments that those who did not. There are also some scientific studies that included physical exercise in the treatment for panic disorder and compared them to other single pharmacological treatments.

So our objective will be to compare the efficacy of a pharmacological monotherapy (alprazolam), that is one of the options for the pharmacological treatment of panic disorder, with other treatment such as the combination of aerobic physical exercise and alprazolam, and to determine if this combination results in a better therapeutic response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy of Aerobic Exercise Added to Alprazolam in Panic Disorder Treatment: a Clinical Randomized Trial
• Actual Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Sep 30, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Alprazolam Patients assigned to the pharmacological plan	Drug: Alprazolam; The patients assigned to the pharmacological plan will receive 4 mg alprazolam daily for 12 weeks. Two weeks after the first interview they have their first baseline psychiatric control, where all the patients are tested. Then, at the same visit, all the patients are indicated 4 mg of alprazolam. The dose is gradually increased from 1 to 4 mg along the first week of treatment. The test is repeated during weeks 2, 4, 8 and 12.; Other Names: Non exercise group
Active Comparator: Alprazolam + Aerobic exercise Patients assigned to mix plan	Drug: Alprazolam + Aerobic exercise; The patients assigned to exercise have to pass an ergometric test to determine their functional capacity expressed in METs for future exercise indication. Two weeks after the first interview they have their first baseline psychiatric control and at the same time they are indicated a 4 mg dose of alprazolam, gradually increased from 1 to 4 mg along the first week of treatment. The test is repeated during weeks 2, 4, 8 and 12. Then they follow a protocolized aerobic exercise plan for this study during 12 weeks. The type of selected exercise consists of a rapid walk for 30 minutes divided in stages. After each stage the patient has to control his own heart frequency that has to be between 50 and 75% of their maximum to assure an aerobic condition (American Cardiological Association).; Other Names: Exercise group

Outcome Measures

Primary Outcome Measures

1. Participants´Endpoint Change From Baseline in Hamilton Anxiety Rating Scale [12 weeks]

   The Hamilton Anxiety Rating Scale is a test that consists of 14 items measuring the severity of anxiety symptoms. Each item is rated on a 5-point ordinal scale, ranging from 0 (not present) to 4 (severe). Each of the 14 items measure both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety)with a total score range of 0-56, where 17 indicates mild severity, 18-24 mild to moderate severity, and 25-30 moderate to severe.

Secondary Outcome Measures

1. Participants´Endpoint Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) [Baseline and 12 weeks]

   The Clinical Global Impression Severity scale is a 7 point ordinal scale that rates the severity of the patient's illness, assessing on the severity of a patient's mental illness. It ranges from 1 to 7 (1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; 7, extremely ill).

2. Participants´Endpoint Change From Baseline in Clinical Global Impression Improvement Scale (CGI-I) [Baseline and 12 weeks]

   The Clinical Global Impression Improvement Scale is a 7 point ordinal scale that assesses how much the patient's illness has improved or worsened relative to a baseline state before the intervention. Rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with panic disorder scored between 20 and 30 by the Hamilton Anxiety Rating Scale/14. (Baseline scale scores were measured during the first interview and diagnoses were made by a psychiatrist using the Structured Clinical Interview for DSM IV).

• Good physical health and normal results determined on a previous physical examination and routine laboratory tests (renal, hepatic, hematological and thyroid function).

• Patients who completed a written informed consent form (which was obtained from every included patient and had been fully explained before the procedure).

Exclusion Criteria:

• A history of some kind of recent somatic disease.

• Diagnosis of some other type of associated or psychiatric disease of axis I of DSM IV, such as affective disorders, drug dependency.

• Hamilton Anxiety Scale lower than 20 points or higher than 30.

• Use of some other type of medication or treatment (including psychotherapy) or having received it during last past 3 months.

• Patients who could not complete the clinical examination

• Patients who have not accepted to complete or sign the written informed consent.

• Pregnant patients or in lactation. (A pregnancy test was performed for women in fertile age)

• Patients with history of rejection to the used drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Psychiatry Academic Unit at J.A.Fernandez Hospital, University of Buenos Aires Medicine School Department of Mental Health	Buenos Aires	Capital Federal	Argentina	1425

Sponsors and Collaborators

• University of Buenos Aires

Investigators

• Principal Investigator: Marcelo G Rudelir, MD, Psychiatry and Mental Health Department at University of Buenos Aires

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Psychiatry and Mental Health Department at University of Buenos Aires

Publications

• Toro Martínez E, Rudelir M. [Assessment of suicide risk: clinical and legal aspects]. Vertex. 2005 May-Jun;16(61):196-205. Review. Spanish.

• Responsible Party: Dr.Marcelo Rudelir, Ph D, University of Buenos Aires
• ClinicalTrials.gov Identifier: NCT00803400
• Other Study ID Numbers: UDHFMEDUBA0709
• First Posted: Dec 5, 2008
• Last Update Posted: Aug 19, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Dr.Marcelo Rudelir, Ph D, University of Buenos Aires: Panic disorder; Exercise; Alprazolam; Aerobic
• Additional relevant MeSH terms: Disease; Panic Disorder; Alprazolam

Study Results

Participant Flow

Recruitment Details	180 patients were preselected for the study and 150 were eligible for the study. They were outpatients from the office practice and were recruited from March 2005 to July 2007.
Pre-assignment Detail	30 selected patients were not included: 12 did not match the 20 points for the Hamilton Anxiety Scale; 10 had history of medical diseases (5 of hypothyroidism, 4 of hypertension, and 1 of chronic fatigue syndrome); 8 had other associated psychiatric diseases: (5 had major depressive disorder and 3 had social anxiety disorder).

Arm/Group Title	Alprazolam	Alprazolam + Aerobic Exercise
Arm/Group Description	Pacients receiving only alprazolam	Pacients receiving alprazolam + aerobic exercise
Period Title: Overall Study
STARTED	75	75
COMPLETED	55	51
NOT COMPLETED	20	24

Baseline Characteristics

Arm/Group Title	Alprazolam	Alprazolam + Aerobic Exercise	Total
Arm/Group Description	Patients receiving only alprazolam	Patients receiving alprazolam + aerobic exercise	Total of all reporting groups
Overall Participants	75	75	150
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	75 100%	75 100%	150 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.01 (8.07)	35.68 (7.67)	34.85 (7.89)
Sex: Female, Male (Count of Participants)
Female	57 76%	55 73.3%	112 74.7%
Male	18 24%	20 26.7%	38 25.3%
Region of Enrollment (participants) [Number]
Argentina	75 100%	75 100%	150 100%

Outcome Measures

1. Primary Outcome

Title	Participants´Endpoint Change From Baseline in Hamilton Anxiety Rating Scale
Description	The Hamilton Anxiety Rating Scale is a test that consists of 14 items measuring the severity of anxiety symptoms. Each item is rated on a 5-point ordinal scale, ranging from 0 (not present) to 4 (severe). Each of the 14 items measure both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety)with a total score range of 0-56, where 17 indicates mild severity, 18-24 mild to moderate severity, and 25-30 moderate to severe.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alprazolam	Alprazolam + Aerobic Exercise
Arm/Group Description	Patients receiving only alprazolam	Patients receiving alprazolam + aerobic exercise
Measure Participants	75	75
Mean (Standard Deviation) [Units on a scale]	22.59 (2.09)	22.73 (1.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alprazolam, Alprazolam + Aerobic Exercise
	Comments	A p-value less than 0.05 (≤ 0.05) is statistically significant. It indicates strong evidence against the null hypothesis, as there is less than a 5% probability the null is correct (and the results are random)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	t-test, 1 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1
	Confidence Interval	(1-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Participants´Endpoint Change From Baseline in Clinical Global Impression Severity Scale (CGI-S)
Description	The Clinical Global Impression Severity scale is a 7 point ordinal scale that rates the severity of the patient's illness, assessing on the severity of a patient's mental illness. It ranges from 1 to 7 (1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; 7, extremely ill).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alprazolam	Alprazolam + Aerobic Exercise
Arm/Group Description	Patients only receiving alprazolam	Patients receiving alprazolam + aerobic exercise
Measure Participants	75	75
Mean (Standard Deviation) [Units on a scale]	4.05 (0.23)	4.06 (0.24)

3. Secondary Outcome

Title	Participants´Endpoint Change From Baseline in Clinical Global Impression Improvement Scale (CGI-I)
Description	The Clinical Global Impression Improvement Scale is a 7 point ordinal scale that assesses how much the patient's illness has improved or worsened relative to a baseline state before the intervention. Rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Patients with history of Panic Disorder

Arm/Group Title	Alprazolam	Alprazolam + Aerobic Exercise
Arm/Group Description	Patients receiving only alprazolam	Patients receiving alprazolam + aerobic exercise
Measure Participants	55	51
Mean (Standard Deviation) [Score on a scale]	2.70 (0.62)	1.86 (0.60)

Adverse Events

Time Frame	Adverse event data were collected for 12 weeks
Adverse Event Reporting Description	Definition of adverse events are similar of those taken from clinicaltrials.gov
Arm/Group Title	Alprazolam		Alprazolam + Aerobic Exercise
Arm/Group Description	Pacients receiving only alprazolam		Pacients receiving alprazolam + aerobic exercise
All Cause Mortality
	Alprazolam		Alprazolam + Aerobic Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Alprazolam		Alprazolam + Aerobic Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/75 (0%)		0/75 (0%)
Other (Not Including Serious) Adverse Events
	Alprazolam		Alprazolam + Aerobic Exercise
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/75 (42.7%)		39/75 (52%)
Nervous system disorders
Somnolence	28/75 (37.3%)	52	34/75 (45.3%)	60
Dizziness	4/75 (5.3%)	8	5/75 (6.7%)	9

Limitations/Caveats

Panic patients may sometimes be reluctant to use medication. This could lead to early drop outs. Possible difficulties in following the exercise protocol.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.